Comparing Inotuzumab Combined With Low Intensity Chemotherapy Plus Blinatumomab to Usual Chemotherapy Plus Blinatumomab in Older Adults With CD22+ B-cell Acute Lymphoblastic Leukemia

July 9, 2026 updated by: Alliance for Clinical Trials in Oncology

A Randomized Phase II Study Testing the Combination of Inotuzumab Ozogamicin and Lower Dose Chemotherapy Plus Blinatumomab Compared to Usual Chemotherapy Plus Blinatumomab for Older Adults With B-Cell Acute Lymphoblastic Leukemia or B-Cell Lymphoblastic Lymphoma

This phase II trial compares the combination of inotuzumab ozogamicin and low intensity chemotherapy and blinatumomab to the usual chemotherapy with blinatumomab in treating patients with B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a drug, called CalichDMH. 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 CalichDMH to kill them. Chemotherapy drugs 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. A monoclonal antibody, such as blinatumomab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving inotuzumab ozogamicin with chemotherapy and blinatumomab may help shrink the cancer and stop it from returning.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare measurable residual disease (MRD) negative event-free survival (EFS) rate of the experimental arm (A) to standard arm (B) with EFS defined as time from randomization to occurrence of an event.

SECONDARY OBJECTIVES:

I. To determine overall response rate (complete response [CR] + complete remission with partial hematologic recovery [CRh] + complete remission with incomplete platelet counts [CRp] + complete remission with incomplete blood count recovery [CRi]) at designated time points (after cycle 1, after cycle 2, end of blinatumomab [blina]-1, end of intensive phase/blina-4) in each treatment arm.

II. To determine rate of flow cytometry MRD-negativity (undetectable or detectable < 10^-4) at designated time points (after cycle 1, after cycle 2, end of blina-1, end of intensive phase/blina-4) in each treatment arm.

III. To compare MRD response by central aspirate multiparameter flow cytometry (Wood lab) Children's Hospital of Los Angeles [CHLA]) to next generation sequencing MRD assessment (clonoSEQ, Adaptive) of blood and bone marrow at designated time points (after cycle 1, after cycle 2, and end of blina-1) and to determine association with outcome, (EFS, disease free survival [DFS], overall survival [OS]) in each treatment arm.

IV. To determine the event-free survival (EFS) standard-definition (event defined as failure to achieve morphologic remission by end of cycle 2, hematologic relapse, death), disease-free survival (DFS), overall survival (OS) of each arm (median, 6-month, 1-year, 2-year, 3-year) in each treatment arm.

V. To determine proportion of patients who proceed to allogeneic transplant after initial response (without intervening salvage therapy) in each treatment arm.

VI. To determine rate of liver toxicity (grade 3-5 alanine aminotransferase [ALT] increase, aspartate aminotransferase [AST] increase, bilirubin increase, alkaline phosphatase increase).

VII. To describe the safety and tolerability of each arm including rate of grade 3-5 non-hematologic toxicity and treatment-related mortality (grade 5 toxicity VIII. To determine rate of delays in intensive-phase chemotherapy due to neutropenia and thrombocytopenia (in responding patients).

IX. To assess the baseline variations in comorbidity burden, physical, nutritional, and cognitive function of the study participants, and explore the association between comorbidity burden, physical, nutritional, and cognitive function, and the outcomes of therapy (grade 3-5 non-hematological toxicities, and OS).

X. To explore the longitudinal changes in physical, nutritional, and cognitive function among the experimental and control groups.

XI. To compare the burden of patient-reported symptomatic adverse events between treatment arms using the Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE).

XII. To correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters.

XIII. To correlate specific karyotype groups with response rates, response duration, MRD, and survival in patients treated on this study.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

INDUCTION/CONSOLIDATION:

*CHEMOTHERAPY (CHEMO) CYCLE 1: Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on days 2 and 8, cyclophosphamide IV over 3 hours every 12 hours (Q12H) on days 1-3, vincristine IV on days 1 and 8, dexamethasone IV or orally (PO) on days 1-4 and 11-14. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8. Patients receive methotrexate intrathecally (IT) on day 2 and cytarabine IT on day 8.

CHEMO CYCLE 2: Patients will receive inotuzumab ozogamicin IV over 1 hour on days 2 and 8, methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8. Patients also receive cytarabine IT on day 2 and methotrexate IT on day 8.

  • BLINA-1 & BLINA-2: Patients receive blinatumomab IV continuously on days 1-28. Patients also receive alternating cytarabine IT and methotrexate IT on days 2 and 8. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. At the end of Cycle 2, patients < 70 years of age proceed to BLINA-3 & BLINA-4 treatment.
  • CHEMO CYCLE 3: Patients receive inotuzumab ozogamicin IV over 1 hour on days 2 and 8, cyclophosphamide IV over 3 hours Q12H on days 1-3, vincristine IV on days 1 and 8, and dexamethasone IV or PO on days 1-4 and 11-14. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8.
  • CHEMO CYCLE 4: Patients receive inotuzumab ozogamicin IV over 1 hour on days 2 and 8, methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8.
  • BLINA-3 & BLINA-4: Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on day 1, prednisone PO daily on days 1-5, mercaptopurine PO twice daily (BID) on days 1-28, and methotrexate PO weekly. Treatment repeats every 28 days for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspiration and blood sample collection throughout the study.

ARM B:

INDUCTION/CONSOLIDATION:

  • CHEMO CYCLE 1: Patients receive cyclophosphamide IV over 3 hours Q12H on days 1-3, doxorubicin IV over 24 hours on day 4, vincristine IV on days 1 and 8, dexamethasone IV or PO on days 1-4 and 11-14. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8. Patients receive methotrexate IT on day 2 and cytarabine IT on day 8.
  • CHEMO CYCLE 2: Patients receive methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8. Patients also receive cytarabine IT on day 2 and methotrexate IT on day 8.
  • BLINA-1 & BLINA-2: Patients receive blinatumomab IV continuously on days 1-28. Patients also receive alternating cytarabine IT and methotrexate IT on days 2 and 8. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. At the end of Cycle 2 patients < 70 years of age, proceed to BLINA-3 & BLINA-4 treatment.
  • CHEMO CYCLE 3: Patients receive cyclophosphamide IV over 3 hours Q12H on days 1-3, doxorubicin IV over 24 hours on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or PO on days 1-4 and 11-14. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8.
  • CHEMO CYCLE 4: Patients receive methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours Q12H on days 2-3, methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing >= 20% CD20 also receive rituximab IV on days 2 and 8.
  • BLINA-3 & BLINA-4: Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on day 1, prednisone PO daily on days 1-5, mercaptopurine PO BID on days 1-28, and methotrexate PO weekly. Treatment repeats every 28 days for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspiration and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 2 months until 1 year after completion of therapy, every 3 months until 2 years after completion of therapy, and then every 6 months until 5 years from study registration.

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • San Juan City Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
    • California
      • Irvine, California, United States, 92612
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Caldwell, Idaho, United States, 83605
        • Saint Alphonsus Cancer Care Center-Caldwell
      • Coeur d'Alene, Idaho, United States, 83814
        • Kootenai Health - Coeur d'Alene
      • Nampa, Idaho, United States, 83687
        • Saint Alphonsus Cancer Care Center-Nampa
      • Post Falls, Idaho, United States, 83854
        • Kootenai Clinic Cancer Services - Post Falls
      • Sandpoint, Idaho, United States, 83864
        • Kootenai Clinic Cancer Services - Sandpoint
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Glenview, Illinois, United States, 60026
        • NorthShore University HealthSystem-Glenbrook Hospital
      • Highland Park, Illinois, United States, 60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • Orland Park, Illinois, United States, 60462
        • University of Chicago Medicine-Orland Park
      • Shiloh, Illinois, United States, 62269
        • Memorial Hospital East
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital-Westwood Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Norton Suburban Hospital and Medical Campus
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Mississippi
      • Southhaven, Mississippi, United States, 38671
        • Baptist Memorial Hospital and Cancer Center-Desoto
    • Missouri
      • City of Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • St Louis, Missouri, United States, 63136
        • Siteman Cancer Center at Christian Hospital
    • Montana
      • Anaconda, Montana, United States, 59711
        • Community Hospital of Anaconda
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Bozeman, Montana, United States, 59715
        • Bozeman Health Deaconess Hospital
      • Great Falls, Montana, United States, 59405
        • Benefis Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Logan Health Medical Center
      • Missoula, Montana, United States, 59804
        • Community Medical Center
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Nebraska Medicine-Bellevue
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68118
        • Nebraska Medicine-Village Pointe
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • Rochester, New York, United States, 14642
        • University of Rochester
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Ontario, Oregon, United States, 97914
        • Saint Alphonsus Cancer Care Center-Ontario
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Baptist Memorial Hospital and Cancer Center-Memphis
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Medical Center-EC Cancer Center
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Minocqua, Wisconsin, United States, 54548
        • Marshfield Medical Center - Minocqua
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)

  • Research bone marrow or peripheral blood submission

    * This bone marrow or peripheral blood submission is mandatory prior to registration/randomization as baseline for real-time MRD analysis. The bone marrow sample should be from the first aspiration (i.e., first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be obtained as soon after pre-registration as possible

  • REGISTRATION ELIGIBILITYCRITERIA (STEP 1)

  • Diagnosis of B-cell acute lymphoblastic leukemia (ALL) per World Health Organization (WHO) 2016 criteria. Patients must have >= 20% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) with <20% blasts in the marrow are permitted.

    * T-cell ALL/LBL, Philadelphia-chromosome positive B-cell (as determined by fluorescence in situ hybridization [FISH], cytogenetics, or reverse transcriptase polymerase chain reaction [RT-PCR]), and Burkitt's like leukemia/lymphoma (mature B-ALL) are not eligible

  • Must be CD22 positive by local assessment (>= 20% by immunohistochemistry or flow cytometry). Patients are eligible regardless of CD20 status but CD20 expression should be assessed at diagnosis by flow cytometry or immunohistochemistry
  • Patients with symptomatic central nervous system (CNS) disease are not eligible. CNS assessment is not required for eligibility determination if asymptomatic
  • Patients must have >= 5% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) without marrow involvement (>= 5% blasts) are not eligible
  • No prior chemotherapy for ALL except for hydroxyurea (no limit), steroids limited to 7 days, ATRA (no limit), vincristine (single dose), and/or intra-thecal chemotherapy. Leukapheresis is permitted. Palliative radiation to doses 24 Gy or less is permitted. Patients being treated with chronic steroids for other reasons (autoimmune disorder, etc.) are eligible
  • Age >= 50 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2. ECOG 3 permitted if related to disease
  • Creatinine =< 2.0 g/dL

  • Total bilirubin =< 1.5 x upper limit of normal (ULN)

    * Except in the event of: 1) Gilbert disease, in which case total bilirubin must be =< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to leukemic infiltration, in which case total bilirubin must be =< 2 x ULN

  • AST / ALT =< 2.5 x upper limit of normal (ULN)
  • Cardiac ejection fraction (as measured by multigated acquisition scan [MUGA] or echocardiogram) > 40%

  • No clinically relevant liver disease (such as cirrhosis, active hepatitis, alcohol use disorder or sinusoidal occlusive syndrome), which in the opinion of the treating physician would make this protocol unreasonably hazardous

    • Patients with known hepatitis B virus (HBV) infection are eligible if they are on effective HBV suppressive therapy with undetectable HBV viral load and there is no clinically relevant liver disease present (related or unrelated to HBV-related liver damage)
    • Patients with known history of hepatitis C virus (HCV) infection are eligible if they have cleared the infection spontaneously or via eradication therapy (HCV viral load undetectable) and there is no clinically relevant liver disease present (related or unrelated to HCV-related liver damage)

  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:

    • Medical condition such as uncontrolled diabetes mellitus, uncontrolled cardiac disease, and uncontrolled pulmonary disease.
    • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
    • Patients with a "currently active" second malignancy other than non-melanoma skin cancers, early stage prostate cancer, cervical carcinoma in situ, or other cancer for which standard of care would be observation (not requiring treatment). Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 1 year, or if the cancer has been surgically resected and considered cured. Patients with a history of multiple myeloma with absence of serum paraprotein for >= 1 year are not considered to have a "currently active" malignancy.
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)

Exclusion Criteria:

  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:

    • Medical condition such as uncontrolled diabetes mellitus, uncontrolled cardiac disease, and uncontrolled pulmonary disease.
    • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
    • Patients with a "currently active" second malignancy other than non-melanoma skin cancers, early stage prostate cancer, cervical carcinoma in situ, or other cancer for which standard of care would be observation (not requiring treatment). Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 1 year, or if the cancer has been surgically resected and considered cured. Patients with a history of multiple myeloma with absence of serum paraprotein for >= 1 year are not considered to have a "currently active" malignancy.
  • REGISTRATION EXCLUSION CRITERIA (STEP 1)
  • Patients with symptomatic central nervous system (CNS) disease are not eligible. CNS assessment is not required for eligibility determination if asymptomatic

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (inotuzumab ozogamicin, chemotherapy)

Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.

Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
Drug: Cytarabine
Given IV
Drug: Cyclophosphamide
Given IV
Drug: Mercaptopurine
Given PO
Drug: Prednisone
Given PO
Drug: Vincristine
Given IV
Biological: Rituximab
Given IV
Biological: Inotuzumab Ozogamicin
Given IV
Drug: Dexamethasone
Given IV or PO
Drug: Methylprednisolone
Given IV
Drug: Methotrexate
Given IV or PO
Active Comparator: Arm B (chemotherapy)

Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.

Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
Drug: Cytarabine
Given IV
Drug: Cyclophosphamide
Given IV
Drug: Mercaptopurine
Given PO
Drug: Prednisone
Given PO
Drug: Vincristine
Given IV
Biological: Rituximab
Given IV
Drug: Doxorubicin
Given IV
Drug: Dexamethasone
Given IV or PO
Drug: Methylprednisolone
Given IV
Drug: Methotrexate
Given IV or PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: From randomization to failure to achieve MRD negative complete response (CR) after two cycles of chemotherapy, relapse, removal from protocol therapy due to toxicity prior to achievement of MRD assessed at 3 months.
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
From randomization to failure to achieve MRD negative complete response (CR) after two cycles of chemotherapy, relapse, removal from protocol therapy due to toxicity prior to achievement of MRD assessed at 3 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: Time from achieving a CR/ complete remission with incomplete blood count recovery (CRi) to the time of relapse and/or death, assessed up to 5 years
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
Time from achieving a CR/ complete remission with incomplete blood count recovery (CRi) to the time of relapse and/or death, assessed up to 5 years
Overall survival
Time Frame: From randomization to the time of death due to any cause, assessed up to 5 years
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
From randomization to the time of death due to any cause, assessed up to 5 years
Complete remission rate
Time Frame: Up to 5 years
The proportion of patients who achieve complete remission 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. In a similar manner, the investigators will also evaluate the overall induction response rates. All evaluable patients will be used for this analysis.
Up to 5 years
Overall response rate
Time Frame: Up to 5 years
Overall response rate (CR/CRi, CR/complete remission with incomplete platelet counts [CRp], CR/complete remission with partial hematologic recovery [CRh]). The proportion of patients who achieve complete remission 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. In a similar manner, the investigators will also evaluate the overall induction response rates. All evaluable patients will be used for this analysis.
Up to 5 years
MRD-negativity rate
Time Frame: Up to end of cycle 8 (1 cycle = 28 days)
MRD-negativity by flow cytometry will be evaluated at designated time point (after cycle 1, after cycle 2, end of intensive phase). Will also compare MRD assessment by centralized aspirate flow cytometry (Wood lab) to next generation sequencing (clonoSEQ, Adaptive) of blood and bone marrow at designated time points; and determine association with outcome.
Up to end of cycle 8 (1 cycle = 28 days)
Event-free survival
Time Frame: Up to 5 years
Event defined as failure to achieve Complete Response (CR)/Complete Remission with Incomplete Blood Count Recovery (CRi)/Complete Remission with Partial Hematological Recovery (CRh)/Complete Remission with Incomplete Platelet Counts (CRp), relapse, death.
Up to 5 years
Rate of grade 3-5 adverse events
Time Frame: Up to 5 years
The proportion of patients experiencing a grade 3+ adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms using Fisher's exact tests.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Marlise R. Luskin, MD, MSCE, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 9, 2023

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

March 18, 2022

First Submitted That Met QC Criteria

March 25, 2022

First Posted (Actual)

March 31, 2022

Study Record Updates

Last Update Posted (Actual)

July 10, 2026

Last Update Submitted That Met QC Criteria

July 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A042001
  • U10CA180821 (U.S. NIH Grant/Contract)
  • NCI-2022-01735 (Registry Identifier: NCI Clinical Trial Reporting Program)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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