Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia

THE STUDY

About this study

This phase III trial studies the side effects of inotuzumab ozogamicin and how well it works when given with frontline chemotherapy in treating patients with newly diagnosed B acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug called ozogamicin. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers ozogamicin to kill them. Chemotherapy drugs, such as \[intervention\], work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin with chemotherapy may work better in treating young adults with B acute lymphoblastic leukemia.

Full official title

A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) With Newly Diagnosed Precursor B-Cell ALL

Detailed description

PRIMARY OBJECTIVES:

I. To confirm tolerability of the combination regimen with the addition of inotuzumab ozogamicin to the pediatric-inspired regimen of cancer and leukemia group B (CALGB) 10403.

II. To determine whether the addition of inotuzumab ozogamicin significantly improves the event-free survival (EFS) in patients who achieve an induction response achieved with the pediatric-inspired regimen of CALGB 10403, without censoring for transplant. (Phase III) III. To determine the safety and tolerability of a reduced dose of inotuzumab ozogamicin and two cycles of blinatumomab added to the pediatric-inspired regimen of CALGB 10403 (Pilor cohort).

SECONDARY OBJECTIVES:

I. To determine the impact of inotuzumab ozogamicin on disease-free (DFS) and overall survival (OS) in patients who achieve an induction response.

II. To determine whether the addition of inotuzumab ozogamicin significantly improves the event-free survival (EFS) in patients who achieve an induction response achieved with the pediatric-inspired regimen of CALGB 10403, with censoring for transplant.

III. To determine the impact of inotuzumab ozogamicin on minimal residual disease (MRD) and correlate this with the EFS, DFS and OS.

IV. To determine the prognosis based on patients' low-density array (LDA) gene signature in terms of EFS, DFS, and OS after treatment with or without inotuzumab ozogamicin when added to the C10403 backbone regimen.

V. To evaluate the toxicity and tolerability of the addition of inotuzumab ozogamicin to the pediatric-inspired regimen of CALGB 10403.

CORRELATIVE SCIENCE OBJECTIVES:

I. To assess both the correlation of MRD post-induction and at sequential timepoints with LDA signature.

II. To evaluate the influence of MRD status (detectable vs. not and as a continuous measure) in relation to EFS both in the univariate setting as well as adjusting for other clinical features including initial white blood cell (WBC), ethnicity, sex and age at diagnosis.

III. To evaluate the impact of inotuzumab ozogamicin (inotuzumab) on the kinetics of MRD during treatment with inotuzumab in patients randomized to the experimental treatment arm.

IV. To perform genomic analyses to identify and evaluate the incidence and clinical significance of recurring novel fusion genes including those associated with the BCR-ABL1-like signature and to correlate with MRD status, CR rate, EFS and OS.

V. To assess whether rs4958351 is correlated with L-asp allergic reaction in the adolescent and young adult (AYA) population.

VI. To assess the incidence of inherited genetic variants in the GR1A1, CEP72, CPA2, TPMT, NUDT15, GRIN3A, GRIK1, and other genes (which can be found using a whole genome association study \[GWAS\]), are correlated with increased rates of target toxicities including peripheral neuropathy, hepatotoxicity, pancreatitis, myelosuppression, neurotoxicity, thrombosis, and osteonecrosis, and correlate with treatment discontinuation and other clinical response parameters including complete response (CR) rate, EFS, and OS.

VII. To evaluate asparaginase pharmacokinetics in adolescents and young adults, and investigate its correlation with toxicities and treatment outcomes.

VIII. To investigate the effect of anti-polyethylene glycol (PEG) and anti-agouti signaling protein (ASP) antibodies (PEG-ASP) on ASP enzyme activity.

IX. To measure adherence to oral 6 mercaptopurine (MP) and methotrexate in AYAs with acute lymphoblastic leukemia (ALL) and to examine sociodemographic and behavioral determinants of adherence.

X. To determine the impact of adherence on risk of relapse among AYAs with ALL. XI. To correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters.

XII. To correlate specific karyotype groups with response rates, response duration, survival, and cure in patients treated on this protocol.

XIII. To correlate specific karyotype groups with MRD. XIV. To determine karyotype changes at relapse and the influence of the type of change (or no change) in karyotype at relapse.

XV. To define the rate, analytical performance, and diagnostic yield of ChromoSeq vs. conventional G-banded karyotyping and fluorescence in situ hybridization (FISH) for B ALL patients in a multicenter setting.

OUTLINE:

COURSE I (REMISSION INDUCTION THERAPY): All patients receive allopurinol orally (PO) once daily until peripheral blasts and extramedullary disease are reduced and cytarabine intrathecally (IT) over 1 minute on day 1. Patients also receive daunorubicin hydrochloride intravenously, over 1 to 30 minutes (IV) and vincristine sulfate IV on days 1, 8, 15 and 22, dexamethasone PO or IV twice daily (BID) on days 1-7 and 15-21, pegaspargase for patients \>21.5 years IV, over 1 to 2 hours on day 4, 5, or 6, or calaspargase pegol IV, over 1 hour, on days 4, 5 or 6 and methotrexate IT over 1 minute on days 8 and 29. Patients with central nervous system (CNS) 3 disease receive methotrexate IT over 1 minute also on days 15 and 22. All patients then undergo bone marrow aspirate and biopsy on day 29.

Patients enrolled prior to Update 8 with response to remission induction therapy are randomized to 1 of 2 arms. Patients enrolled after amendment 8 are assigned to the pilot cohort. Patients with no response are omitted from the study.

ARM I (CLOSED 7/23/2025):

COURSE II (REMISSION CONSOLIDATION CHEMOTHERAPY): Patients receive cyclophosphamide IV on days 1 and 29, cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, and vincristine sulfate IV, over 1 to 10 minutes on days 15, 22, 43, and 50. Patients \>21.5 years also receive pegaspargase IV, over 1 to 2 hours, on days 15 and 43 and patients \<21.5 years old receive calaspargase pegol IV, over 1 hour, on days 2 and 22, and methotrexate IT on days 1, 8, 15, and 22. Patients with CNS3 receive methotrexate IT only on days 1 and 8. CD20 positive (+) patients receive rituximab IV on days 1, 8, 29, and 36. Patients with evidence of testicular disease at diagnosis also receive radiation therapy (RT). Patients who are MRD+ and CD19+ after completion of this course receive dexamethasone IV or PO on day 1 and blinatumomab IV via continuous infusion on days 1-28, followed by a 14 day break. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo bone marrow aspirate and biopsy on day 56.

COURSE III (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV, over 1 to 10 minutes, on days 1, 11, 21, 31, and 41, methotrexate IV, over 24 hours, and IT on days 1, 11, 21, 31, and 41, patients \>21.5 years old receive pegaspargase IV, over 1 to 2 hours, and patients \< 21.5 years old receive calaspargase pegol IV, over 1 hour on days 2 and 22. CD20+ patients receive rituximab IV on days 1 and 11.

COURSE IV (DELAYED INTENSIFICATION): Patients receive vincristine sulfate IV, over 1 to 10 minutes, on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1-7 and 15-21, doxorubicin IV, over 3 to 60 minutes, on days 1, 8, and 15, patients \>21.5 years old receive pegaspargase IV, over 1 to 2 hours, on day 4, 5, or 6 and day 43, patients \<21.5 years old receive calaspargase pegol IV, over 1 hour, on days 2 and 22. Patients also receive cyclophosphamide IV on day 29, cytarabine IV or SC on days 29-32 and 36-39, thioguanine PO on days 29-42 and methotrexate IT on days 1, 29, and 36. CD20+ patients receive rituximab IV on days 1 and 8. Patients then undergo bone marrow aspirate and biopsy one week after completion of course IV.

COURSE V (MAINTENANCE THERAPY): Patients receive vincristine sulfate IV, over 1 to 10 minutes, on days 1, 29, and 57, dexamethasone PO or IV BID on days 1-5, 29-33, and 57-61, and mercaptopurine PO on days 1-84. Patients also receive methotrexate IT or PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for up to 3 years in the absence of disease progression or unacceptable toxicity.

Patients undergo multigated acquisition scan (MUGA) or echocardiography and x ray imaging during screening, bone marrow aspiration and biopsy and lumbar puncture and blood sample collection throughout the study.

ARM II (CLOSED 7/23/2025): Patients receive inotuzumab ozogamicin IV, over 1 hour, on days 1, 8, and 15 and undergo bone marrow aspirate and biopsy on day 28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who are MRD+ and CD19+ after completion of 2 cycles of inotuzumab ozogamicin receive dexamethasone IV or PO on day 1 and blinatumomab IV via continuous infusion on days 1-28, followed by a 14 day break. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive remission consolidated chemotherapy, interim maintenance chemotherapy, delayed intensification, and maintenance therapy as in Arm I.

Patients undergo MUGA or echocardiography and x ray imaging during screening, bone marrow aspiration and biopsy and lumbar puncture and blood sample collection throughout the study.

PILOT COHORT: Patients receive inotuzumab ozogamicin IV, over 1 hour, on days 1, 8, and 15 and undergo bone marrow aspirate and biopsy on day 28.

COURSE II (REMISSION CONSOLIDATION CHEMOTHERAPY): Patients receive cyclophosphamide IV on days 1 and 29, cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, and vincristine sulfate IV, over 1 to 10 minutes, on days 15, 22, 43, and 50. Patients \> 21.5 years old also receive pegaspargase IV, over 1 to 2 hours, on days 15 and 43 and patients \< 21.5 years old receive calaspargase pegol IV, over 1 hour, on days 15 and 43, and methotrexate IT on days 1, 8, 15, and 22. Patients with CNS3 receive methotrexate IT only on days 1 and 8. CD20+ patients receive rituximab IV on days 1, 8, 29, and 36. Patients with evidence of testicular disease at diagnosis also receive RT. Patients then undergo bone marrow aspirate and biopsy on day 56.

BLINATUMOMAB: Patients receive blinatumomab IV, continuously, on days 1-28 of one 42-day cycle in the absence of disease progression or unacceptable toxicity. Patients also receive dexamethasone PO or IV prior to starting the blinatumomab cycle, and a single dose of methotrexate IT between cycle days 29 and 42.

COURSE III (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV, over 1 to 10 minutes, on days 1, 11, 21, 31, and 41, methotrexate IV, over 24 hours, and IT on days 1, 11, 21, 31, and 41, patients \>21.5 years old receive pegaspargase IV, over 1 to 2 hours, and patients \< 21.5 years old receive calaspargase pegol IV, over 1 hour on days 2 and 22. CD20+ patients receive rituximab IV on days 1 and 11.

BLINATUMOMAB: Patients receive blinatumomab IV, continuously, on days 1-28 of one 42-day cycle in the absence of disease progression or unacceptable toxicity. Patients also receive dexamethasone PO or IV prior to starting the blinatumomab cycle, and a single dose of methotrexate IT between cycle days 29 and 42. Patients who are MRD positive and CD19+ after Course II may continue to receive blinatumomab IV, continuously on days 1-28 of each cycle. Cycles repeat every 42 days for an additional 2 cycles in the absence of disease progression or unacceptable toxicity, per investigator discretion.

COURSE IV (DELAYED INTENSIFICATION): Patients receive vincristine sulfate IV, over 1 to 10 minutes on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1-7 and 15-21, doxorubicin IV, over 3 to 60 minutes, on days 1, 8, and 15, patients \> 21.5 years old receive pegaspargase IV, over 1 to 2 hours, on day 4, 5, or 6 and day 43, patients \< 21.5 years old receive calaspargase pegol IV, over 1 hour, on day 4, 5, or 6 and 43. Patients also receive cyclophosphamide IV on day 29, cytarabine IV or SC on days 29-32 and 36-39, thioguanine PO on days 29-42 and methotrexate IT on days 1, 29, and 36. CD20+ patients receive rituximab IV on days 1 and 8. Patients then undergo bone marrow aspirate and biopsy one week after completion of course IV.

COURSE V (MAINTENANCE THERAPY): Patients receive vincristine sulfate IV, over 1 to 10 minutes on days 1, 29, and 57, dexamethasone PO or IV BID on days 1-5, 29-33, and 57-61, and mercaptopurine PO on days 1-84. Patients also receive methotrexate IT on day 1 of cycles 1-4 and PO once weekly (QW) of each cycle. Treatment repeats every 12 weeks for up to 3 years in the absence of disease progression or unacceptable toxicity.

Patients undergo MUGA or echocardiography and x ray imaging during screening, bone marrow aspiration and biopsy and lumbar puncture and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 2 months for 2 years, every 3 months 2 years, and then every 6 months for up to 10 years.

PARTICIPATION

Who may participate

Minimum age: 18 Years
Maximum age: 39 Years
Sex eligibility: All sexes
Healthy volunteers: Not accepted

Only the study team can confirm eligibility. The registry criteria below are not a medical recommendation.

Full inclusion and exclusion criteria

Inclusion Criteria:

REGISTRATION ELIGIBILITY CRITERIA (STEP 1)

* Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (WHO criteria) are eligible. Patients with Burkitt type ALL are NOT eligible
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; systemic chemotherapy must begin within 72 hours of this intrathecal therapy
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Age \>= 18 years and \< 40 years
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN), unless suspected leukemic involvement of the liver
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Direct bilirubin =\< 3 x upper limit of normal (ULN), unless suspected leukemic involvement of the liver
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Calculated (calc.) creatinine clearance \>= 50 mL/min by Cockcroft-Gault
* RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) CONFIRMATION OF TOLERABILITY AND PHASE III ONLY): Completion of remission induction therapy
* RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) CONFIRMATION OF TOLERABILITY AND PHASE III ONLY):Patients with M2 marrow or better are eligible; patients with M3 or M4 marrow (greater than 25% lymphoblasts) will not be eligible to be randomized

* Rating: M0, M1; Blast Cells (%): 0-5.0
* Rating: M2; Blast Cells (%): 5.1-25.0
* Rating: M3; Blast Cells (%): \> 25-50
* Rating: M4; Blast Cells (%): \> 50.0
* The term "blast cell" includes any cell that cannot be classified as a more mature normal element, and includes "leukemic cells," pathologic lymphocytes, and stem cells
* RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE III ONLY): Absolute neutrophil count (ANC) \>= 750/mm\^3
* RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE III ONLY): Platelet count \>= 75,000/mm\^3
* RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE III ONLY): Total bilirubin =\< 1.5 x upper limit of normal (ULN), except for patients with known Gilbert's syndrome
* RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE III ONLY): Aspartate aminotransferase (AST) =\< 8 x upper limit of normal (ULN)

EXCLUSION CRITERIA

* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients who have BCR-ABL fusion transcript determined by fluorescence in situ hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction; please note: patients must also be assessed for CD20 positivity and other markers; positivity for CD22 and CD20 is defined as baseline expression of the CD22 or CD20 antigen in more than 20% of leukemic cells using local multiparameter flow-cytometric immunophenotyping with the use of CD45 expression as a marker to gate the ALL blast population, according to recommendations from the European LeukemiaNet
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior therapy for ALL except for limited treatment (=\< 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine; however, patients who are being treated with chronic steroids for other reasons (for example, to treat asthma, autoimmune disorders, lupus, etc.) are eligible
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study involves agents that have known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =\< 8 days prior to registration is required
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with down syndrome are excluded from this study due to the likelihood of excessive toxicity resulting; these patients should be treated in consultation with a pediatric oncologist

Suspended

Fort Smith, Arkansas, 72903, United States

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Kaiser Permanente-Deer Valley Medical Center

Recruiting

Antioch, California, 94531, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

PCR Oncology

Suspended

Arroyo Grande, California, 93420, United States

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Providence Saint Joseph Medical Center/Disney Family Cancer Center

Suspended

Burbank, California, 91505, United States

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Community Cancer Institute

Recruiting

Clovis, California, 93611, United States

Site contacts (2)

Site Public ContactContactPhone: 559-387-1827

Mohammed S. BukariPrincipal investigator

University Oncology Associates

Suspended

Clovis, California, 93611, United States

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UC Irvine Health Cancer Center-Newport

Recruiting

Costa Mesa, California, 92627, United States

Site contacts (2)

Site Public ContactContactPhone: 877-827-8839

Deepa JeyakumarPrincipal investigator

Kaiser Permanente Dublin

Recruiting

Dublin, California, 94568, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691

Jennifer M. SugaPrincipal investigator

Kaiser Permanente-Fremont

Recruiting

Fremont, California, 94538, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Suspended

Oakland, California, 94611, United States

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Kaiser Permanente-Oakland

Recruiting

Oakland, California, 94611, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, 92868, United States

Site contacts (2)

Site Public ContactContactPhone: 877-827-8839Email: ucstudy@uci.edu

Deepa JeyakumarPrincipal investigator

Stanford Cancer Institute Palo Alto

Recruiting

Palo Alto, California, 94304, United States

Site contacts (2)

Site Public ContactContactPhone: 650-498-7061Email: cancertrialsinfo@stanford.edu

Michaela LiedtkePrincipal investigator

Kaiser Permanente-Rancho Cordova Cancer Center

Suspended

Rancho Cordova, California, 95670, United States

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Recruiting

Sacramento, California, 95814, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: kpoct@kp.org

Jennifer M. SugaPrincipal investigator

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, 95817, United States

Site contacts (2)

Site Public ContactContactPhone: 916-734-3089

Brian A. JonasPrincipal investigator

Kaiser Permanente-South Sacramento

Recruiting

Sacramento, California, 95823, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

South Sacramento Cancer Center

Suspended

Sacramento, California, 95823, United States

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Kaiser Permanente Sacramento Medical Center

Suspended

Sacramento, California, 95825, United States

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Kaiser Permanente-San Francisco

Recruiting

San Francisco, California, 94115, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Kaiser Permanente-Santa Teresa-San Jose

Recruiting

San Jose, California, 95119, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Kaiser Permanente San Leandro

Recruiting

San Leandro, California, 94577, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Kaiser Permanente-San Rafael

Suspended

San Rafael, California, 94903, United States

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Kaiser San Rafael-Gallinas

Recruiting

San Rafael, California, 94903, United States

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Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Kaiser Permanente Medical Center - Santa Clara

Recruiting

Santa Clara, California, 95051, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Kaiser Permanente-Santa Rosa

Recruiting

Santa Rosa, California, 95403, United States

Site contacts (2)

Site Public ContactContactPhone: 877-642-4691Email: Kpoct@kp.org

Jennifer M. SugaPrincipal investigator

Suspended

Honolulu, Hawaii, 96813, United States

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Queen's Cancer Cenrer - POB I

Suspended

Honolulu, Hawaii, 96813, United States

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Queen's Medical Center

Suspended

Honolulu, Hawaii, 96813, United States

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Straub Clinic and Hospital

Recruiting

Wilcox Memorial Hospital and Kauai Medical Clinic

Suspended

Lihue, Hawaii, 96766, United States

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Hawaii Cancer Care - Westridge

Suspended

‘Aiea, Hawaii, 96701, United States

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Pali Momi Medical Center

Recruiting

‘Aiea, Hawaii, 96701, United States

Site contacts (2)

Site Public ContactContactPhone: 808-486-6000

Craig S. BoddyPrincipal investigator

Queen's Cancer Center - Pearlridge

Suspended

‘Aiea, Hawaii, 96701, United States

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The Cancer Center of Hawaii-Pali Momi

Suspended

‘Aiea, Hawaii, 96701, United States

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Saint Alphonsus Cancer Care Center-Boise

Recruiting

Boise, Idaho, 83706, United States

Site contacts (2)

Site Public ContactContactPhone: 734-712-3671Email: stephanie.couch@stjoeshealth.org

Tareq Al baghdadiPrincipal investigator

Saint Luke's Cancer Institute - Boise

Suspended

Boise, Idaho, 83712, United States

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Saint Alphonsus Cancer Care Center-Caldwell

Recruiting

Caldwell, Idaho, 83605, United States

Site contacts (2)

Site Public ContactContactPhone: 734-712-3671Email: stephanie.couch@stjoeshealth.org

Tareq Al baghdadiPrincipal investigator

Kootenai Health - Coeur d'Alene

Recruiting

Saint Luke's Cancer Institute - Nampa

Suspended

Nampa, Idaho, 83687, United States

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Kootenai Clinic Cancer Services - Post Falls

Recruiting

Post Falls, Idaho, 83854, United States

Site contacts (2)

Site Public ContactContactPhone: 406-969-6060Email: mccinfo@mtcancer.org

John M. SchallenkampPrincipal investigator

Kootenai Clinic Cancer Services - Sandpoint

Recruiting

Sandpoint, Idaho, 83864, United States

Site contacts (2)

Site Public ContactContactPhone: 406-969-6060Email: mccinfo@mtcancer.org

John M. SchallenkampPrincipal investigator

Saint Luke's Cancer Institute - Twin Falls

Suspended

Twin Falls, Idaho, 83301, United States

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OSF Saint Anthony's Health Center

Suspended

Alton, Illinois, 62002, United States

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Suspended

Homer Glen, Illinois, 60491, United States

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Northwestern Medicine Lake Forest Hospital

Active, not recruiting

Lake Forest, Illinois, 60045, United States

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Recruiting

Iowa City, Iowa, 52242, United States

Site contacts (2)

Site Public ContactContactPhone: 800-237-1225

Grerk SutamtewagulPrincipal investigator

Methodist West Hospital

Active, not recruiting

West Des Moines, Iowa, 50266-7700, United States

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Suspended

Wichita, Kansas, 67214, United States

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Cancer Center of Kansas - Wichita

Recruiting

Wichita, Kansas, 67214, United States

Site contacts (2)

Site Public ContactContactPhone: 316-291-4774Email: research@viachristi.org

Dennis F. MoorePrincipal investigator

Wesley Medical Center

Suspended

Wichita, Kansas, 67214, United States

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University of Kentucky/Markey Cancer Center

Recruiting

Massachusetts General Hospital Cancer Center

Suspended

Boston, Massachusetts, 02114, United States

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Beth Israel Deaconess Medical Center

Suspended

Boston, Massachusetts, 02215, United States

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Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, 02215, United States

Site contacts (2)

Site Public ContactContactPhone: 877-442-3324

Daniel J. DeAngeloPrincipal investigator

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Recruiting

Ann Arbor, Michigan, 48106, United States

Site contacts (2)

Site Public ContactContactPhone: 734-712-7251Email: MCRCwebsitecontactform@stjoeshealth.org

Tareq Al baghdadiPrincipal investigator

Suspended

Caro, Michigan, 48723, United States

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Chelsea Hospital

Recruiting

Chelsea, Michigan, 48118, United States

Site contacts (2)

Site Public ContactContactPhone: 734-712-7251Email: MCRCwebsitecontactform@stjoeshealth.org

Tareq Al baghdadiPrincipal investigator

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Recruiting

Chelsea, Michigan, 48118, United States

Site contacts (2)

Site Public ContactContactPhone: 734-712-7251Email: MCRCwebsitecontactform@stjoeshealth.org

Tareq Al baghdadiPrincipal investigator

Hematology Oncology Consultants-Clarkston

Suspended

Clarkston, Michigan, 48346, United States

Study team contact · shared across sites

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Hurley Medical Center

Recruiting

Flint, Michigan, 48503, United States

Site contacts (2)

Site Public ContactContactPhone: 810-762-8038Email: wstrong@ghci.org

Tareq Al baghdadiPrincipal investigator

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Recruiting

Recruiting

Kalamazoo, Michigan, 49007, United States

Site contacts (2)

Site Public ContactContactPhone: 616-391-1230Email: crcwm-regulatory@crcwm.org

Kathleen Y. ButlerPrincipal investigator

West Michigan Cancer Center

Recruiting

Henry Ford Saint John Hospital - Macomb Medical

Recruiting

Macomb, Michigan, 48044, United States

Site contacts (2)

Site Public ContactContactPhone: 313-343-3166Email: kforman1@hfhs.org

Tareq Al baghdadiPrincipal investigator

Henry Ford Warren Hospital - Breast Macomb

Suspended

Macomb, Michigan, 48044, United States

Study team contact · shared across sites

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Saint Mary's Oncology/Hematology Associates of Marlette

Suspended

Marlette, Michigan, 48453, United States

Study team contact · shared across sites

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Trinity Health Muskegon Hospital

Suspended

Muskegon, Michigan, 49444, United States

Study team contact · shared across sites

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Corewell Health Lakeland Hospitals - Niles Hospital

Recruiting

Corewell Health Reed City Hospital

Recruiting

Reed City, Michigan, 49677, United States

Site contacts (2)

Site Public ContactContactPhone: 616-391-1230Email: crcwm-regulatory@crcwm.org

Kathleen Y. ButlerPrincipal investigator

Henry Ford Rochester Hospital

Suspended

Rochester Hills, Michigan, 48309, United States

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MyMichigan Medical Center Saginaw

Suspended

Saginaw, Michigan, 48601, United States

Study team contact · shared across sites

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Oncology Hematology Associates of Saginaw Valley PC

Suspended

Saginaw, Michigan, 48604, United States

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Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Recruiting

Saint Joseph, Michigan, 49085, United States

Site contacts (2)

Site Public ContactContactPhone: 616-391-1230Email: crcwm-regulatory@crcwm.org

Kathleen Y. ButlerPrincipal investigator

Corewell Health Lakeland Hospitals - Saint Joseph Hospital

Suspended

Saint Joseph, Michigan, 49085, United States

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Bhadresh Nayak MD PC-Sterling Heights

Suspended

Sterling Heights, Michigan, 48312, United States

Study team contact · shared across sites

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MyMichigan Medical Center Tawas

Suspended

Tawas City, Michigan, 48764, United States

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Munson Medical Center

Recruiting

Huron Gastroenterology PC

Recruiting

Ypsilanti, Michigan, 48106, United States

Site contacts (2)

Site Public ContactContactPhone: 734-712-7251Email: MCRCwebsitecontactform@stjoeshealth.org

Tareq Al baghdadiPrincipal investigator

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Recruiting

Abbott-Northwestern Hospital

Recruiting

Recruiting

Siteman Cancer Center at West County Hospital

Recruiting

Recruiting

Hope Cancer Care of Nevada-Pahrump

Suspended

Pahrump, Nevada, 89048, United States

Study team contact · shared across sites

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Renown Regional Medical Center

Suspended

Reno, Nevada, 89502, United States

Study team contact · shared across sites

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Saint Mary's Regional Medical Center

Suspended

Reno, Nevada, 89503, United States

Study team contact · shared across sites

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Radiation Oncology Associates

Suspended

Reno, Nevada, 89509, United States

Study team contact · shared across sites

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Active, not recruiting

Stony Brook, New York, 11794, United States

Study team contact · shared across sites

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State University of New York Upstate Medical University

Active, not recruiting

Syracuse, New York, 13210, United States

Study team contact · shared across sites

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Upstate Cancer Center at Verona

Active, not recruiting

Verona, New York, 13478, United States

Study team contact · shared across sites

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UNC Lineberger Comprehensive Cancer Center

Suspended

Redmond, Oregon, 97756, United States

Study team contact · shared across sites

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Lehigh Valley Hospital-Cedar Crest

Recruiting

Allentown, Pennsylvania, 18103, United States

Site contacts (2)

Site Public ContactContactPhone: 610-402-9543Email: Morgan_M.Horton@lvhn.org

Tareq Al baghdadiPrincipal investigator

Lehigh Valley Hospital - Muhlenberg

Recruiting

Bethlehem, Pennsylvania, 18017, United States

Site contacts (2)

Site Public ContactContactPhone: 610-402-9543Email: Morgan_M.Horton@lvhn.org

Tareq Al baghdadiPrincipal investigator

Pocono Medical Center

Suspended

East Stroudsburg, Pennsylvania, 18301, United States

Study team contact · shared across sites

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Lehigh Valley Hospital-Hazleton

Suspended

Hazleton, Pennsylvania, 18201, United States

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University of Pennsylvania/Abramson Cancer Center

Recruiting

Recruiting

Easley, South Carolina, 29640, United States

Site contacts (2)

Site Public ContactContactPhone: 864-522-4317Email: Kim.Williams3@prismahealth.org

Ki Y. ChungPrincipal investigator

Saint Francis Hospital

Recruiting

Greenville, South Carolina, 29601, United States

Site contacts (2)

Site Public ContactContactPhone: 864-603-6234Email: Heather_Rich@bshsi.org

Stephen H. DyarPrincipal investigator

LDS Hospital

Suspended

Salt Lake City, Utah, 84143, United States

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Saint George Regional Medical Center

Suspended

St. George, Utah, 84770, United States

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Inova Schar Cancer Institute

Active, not recruiting

Fairfax, Virginia, 22031, United States

Study team contact · shared across sites

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Inova Fairfax Hospital

Active, not recruiting

Falls Church, Virginia, 22042, United States

Study team contact · shared across sites

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VCU Massey Comprehensive Cancer Center

Recruiting

Recruiting

Halifax, Nova Scotia, B3H 2Y9, Canada

Site contacts (2)

Site Public ContactContactPhone: 902-473-6000

Nicholas A. ForwardPrincipal investigator

Ottawa Hospital and Cancer Center-General Campus

Recruiting

Ottawa, Ontario, K1H 8L6, Canada

Site contacts (2)

Site Public ContactContactPhone: 613-761-4395

Jill FulcherPrincipal investigator

Jewish General Hospital

Suspended

Montreal, Quebec, H3T 1E2, Canada

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WHAT IS BEING STUDIED

Treatments and study groups

Interventions

AllopurinolDrug

Given PO

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

CytarabineDrug

Given IT, IV, SC

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Daunorubicin HydrochlorideDrug

Given IV

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Vincristine SulfateDrug

Given IV

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

DexamethasoneDrug

Given PO or IV

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Pegylated L-AsparaginaseDrug

Given IV

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

MethotrexateDrug

Given IT, IV, PO

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Bone Marrow Aspiration and BiopsyProcedure

Undergo bone marrow aspiration and biopsy

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

CyclophosphamideDrug

Given IV

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

MercaptopurineDrug

Given PO

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

RituximabBiological

Given IV

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

DoxorubicinDrug

Given IV

Study groups: Arm II (frontline chemotherapy, inotuzumab ozogamicin)

ThioguanineDrug

Given PO

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Inotuzumab OzogamicinBiological

Given IV

Study groups: Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Laboratory Biomarker AnalysisOther

Correlative studies

Study groups: Arm I (frontline chemotherapy), Arm II (frontline chemotherapy, inotuzumab ozogamicin)

Study groups

Arm I (frontline chemotherapy)Active comparator

See detailed description.

Interventions: Drug: Allopurinol, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Vincristine Sulfate, Drug: Dexamethasone, Drug: Pegylated L-Asparaginase, Drug: Methotrexate, Procedure: Bone Marrow Aspiration and Biopsy, Drug: Cyclophosphamide, Drug: Mercaptopurine, Biological: Rituximab, Drug: Thioguanine, Other: Laboratory Biomarker Analysis

Arm II (frontline chemotherapy, inotuzumab ozogamicin)Experimental

Patients receive inotuzumab ozogamicin IV on days 1, 8, and 15 and undergo bone marrow aspirate and biopsy on day 28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who are MRD+ and CD19+ after completion of 2 cycles of inotuzumab ozogamicin receive dexamethasone IV or PO on day 1 and blinatumomab IV via continuous infusion on days 1-28, followed by a 14 day break. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive remission consolidated chemotherapy, interim maintenance chemotherapy, delayed intensification, and maintenance therapy as in Arm I. Patients undergo MUGA or echocardiography and x ray imaging during screening, bone marrow aspiration and biopsy and lumbar puncture and blood sample collection throughout the study.

RESEARCH DETAILS

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Study model: Parallel
Masking: None (open label)
Enrolment: 303 participants · Estimated

TIMELINE & MEASURES

Dates and outcomes

Study started: 20 Sep 2017 · Actual
Primary completion: 1 Nov 2027 · Estimated
Study completion: 1 Apr 2028 · Estimated
First registered: 12 May 2017 · Actual
Last registry update: 19 Oct 2026 · Actual
Status last verified: Oct 2026

Primary outcomes (1)

Event-free survival (EFS)

The EFS distributions between the two arms will be compared using non-stratified log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. with diagnostics test on proportional hazard assumptions first. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.

Time frame: Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years

Secondary outcomes (7)

Disease-free survival (DFS)

Not reported.

Time frame: Time from achievement of complete response (CR) to the time of relapse and/or death, assessed up to 10 years

Overall Survival (OS)

Will be evaluated using Kaplan-Meier as well as Cox regression models.

Time frame: Time from randomization to the time of death due to any cause, assessed up to 10 years

Proportion of patients who achieve CR or any response to induction therapy

Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.

Time frame: Up to 10 years

Overall induction response rates

Time frame: Up to 10 years

Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 5.0

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms. Tolerability of the treatment arms will be assessed through assessing the number of patients who required dose modifications and/or dose delays.

Time frame: Up to 10 years

Proportion of patients who go off treatment due to adverse reactions

Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

Time frame: Up to 10 years

Proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial

Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

Time frame: Up to 10 years

STUDY TEAM

Sponsor and contacts

Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor type: Other
Collaborators: National Cancer Institute (NCI)
Organisation study ID: A041501

Central study contacts

Daniel J. DeAngelo, MD, PhDContactPhone: 617-632-2645Email: daniel_deangelo@dfci.harvard.edu

Study officials

daniel_deangelo@dfci.harvard.edu J. DeAngelo, MD, PhDStudy chair · Dana-Farber Cancer Institute

Contacts are provided by the registry for study enquiries. Do not use these details for marketing or promotions.

Results, documents and references

No results are posted in this registry record

This does not mean the study has no findings. Results may not yet have been submitted or published here.

No study documents are listed in this record.

Publications (2)

Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067. PubMed ↗
Seftel MD. Hyper-CVAD: a regimen for all seasons. Lancet Haematol. 2020 Jul;7(7):e501-e502. doi: 10.1016/S2352-3026(20)30179-4. No abstract available. PubMed ↗