Testing the Combination of Inotuzumab Ozogamicin and Lower Dose Chemotherapy Compared to Usual Chemotherapy for Adults With B-Cell Acute Lymphoblastic Leukemia or B-Cell Lymphoblastic Lymphoma
NCT ID: NCT05303792
Last Updated: 2025-04-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
68 participants
INTERVENTIONAL
2023-06-09
2028-05-31
Brief Summary
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Detailed Description
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I. To compare undetectable measurable residual disease (MRD) 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 \[CR\], CR + complete remission with incomplete platelet counts \[CRp\], CR + complete remission with partial hematologic recovery \[CRh\], CR + complete remission with incomplete blood count recovery \[CRi\]) at designated time points (after cycle 1, after cycle 2, end of intensive phase) 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 intensive phase) in each treatment arm.
III. To compare MRD response by central aspirate multiparameter flow cytometry (Wood lab) 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 intensive phase) and to determine association with outcome, in each treatment arm.
IV. To determine the event-free survival (EFS) standard-definition (event defined as failure to achieve morphologic remission by 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: Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours (Q12H) on days 1-3 of cycles 1, 3, 5, and 7, vincristine IV on days 1 and 8 of cycle 1, 3, 5, and 7, dexamethasone IV or orally (PO) on days 1-4 and 11-14 of cycles 1, 3, 5, and 7, inotuzumab ozogamicin IV over 1 hour on days 2 and 8 of cycles 1-4, methotrexate IV over 24 hours on day 1 of cycles 2, 4, 6, and 8, cytarabine IV over 3 hours Q12H on days 2-3 of cycles 2, 4, 6, and 8, 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 of cycles 1-4. For patients \>= 70 years of age, treatment repeats every 28 days for 2 cycles (an additional 2 cycles may be given at the discretion of the principal investigator \[PI\]) in the absence of disease progression or unacceptable toxicity. For patients \< 70 years of age, treatment repeats every 28 days for 8 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.
ARM B:
INDUCTION: Patients receive cyclophosphamide IV over 3 hours Q12H on days 1-3 of cycle 1, 3, 5, and 7, vincristine IV on days 1 and 8 of cycles 1, 3, 5, and 7, dexamethasone IV or PO on days 1-4 and 11-14 of cycle 1, 3, 5, and 7, doxorubicin IV over 24 hours on day 4 of cycles 1, 3, 5, and 7, methotrexate IV over 24 hours on day 1 of cycles 2, 4, 6, and 8, cytarabine IV over 3 hours Q12H on days 2-3 of cycles 2, 4, 6, and 8, and methylprednisolone IV over 2 hours Q12H on days 1-3 of cycles 2, 4, 6, and 8. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For patients \>= 70 years of age, treatment repeats every 28 days for 2 cycles (an additional 2 cycles may be given at the discretion of the PI) in absence of disease progression or unacceptable toxicity. For patients \< 70 years of age, treatment repeats every 28 days for 8 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.
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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Cyclophosphamide
Given IV
Vincristine
Given IV
Dexamethasone
Given IV or PO
Inotuzumab Ozogamicin
Given IV
Methotrexate
Given IV or PO
Cytarabine
Given IV
Methylprednisolone
Given IV
Rituximab
Given IV
Prednisone
Given PO
Mercaptopurine
Given PO
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.
Cyclophosphamide
Given IV
Vincristine
Given IV
Dexamethasone
Given IV or PO
Methotrexate
Given IV or PO
Cytarabine
Given IV
Methylprednisolone
Given IV
Rituximab
Given IV
Prednisone
Given PO
Mercaptopurine
Given PO
Doxorubicin
Given IV
Interventions
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Cyclophosphamide
Given IV
Vincristine
Given IV
Dexamethasone
Given IV or PO
Inotuzumab Ozogamicin
Given IV
Methotrexate
Given IV or PO
Cytarabine
Given IV
Methylprednisolone
Given IV
Rituximab
Given IV
Prednisone
Given PO
Mercaptopurine
Given PO
Doxorubicin
Given IV
Eligibility Criteria
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Inclusion Criteria
* 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
* Diagnosis of B-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) per World Health Organization (WHO) 2016 criteria. Patients must have \>= 5% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) without measurable marrow involvement (\>= 5% blasts) are not eligible
\* 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 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, or alcohol use disorder), 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)
* 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
* 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.
* Patients with symptomatic central nervous system (CNS) disease are not eligible. CNS assessment is not required for eligibility determination if asymptomatic
50 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Alliance for Clinical Trials in Oncology
OTHER
Responsible Party
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Principal Investigators
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Marlise R. Luskin, MD, MSCE
Role: STUDY_CHAIR
Dana-Farber Cancer Institute
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Yale University
New Haven, Connecticut, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
Memorial Hospital East
Shiloh, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
Norton Suburban Hospital and Medical Campus
Louisville, Kentucky, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
Community Hospital of Anaconda
Anaconda, Montana, United States
Billings Clinic Cancer Center
Billings, Montana, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, United States
Logan Health Medical Center
Kalispell, Montana, United States
Community Medical Center
Missoula, Montana, United States
Nebraska Medicine-Bellevue
Bellevue, Nebraska, United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Northwell Health/Center for Advanced Medicine
Lake Success, New York, United States
North Shore University Hospital
Manhasset, New York, United States
Mount Sinai Hospital
New York, New York, United States
University of Rochester
Rochester, New York, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, United States
Providence Portland Medical Center
Portland, Oregon, United States
Providence Saint Vincent Medical Center
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, United States
University of Vermont Medical Center
Burlington, Vermont, United States
University of Vermont and State Agricultural College
Burlington, Vermont, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
West Virginia University Healthcare
Morgantown, West Virginia, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, United States
San Juan City Hospital
San Juan, , Puerto Rico
Countries
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Other Identifiers
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NCI-2022-01735
Identifier Type: REGISTRY
Identifier Source: secondary_id
A042001
Identifier Type: -
Identifier Source: org_study_id
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