Ignite Creation Date:
2025-12-24 @ 3:15 PM
Ignite Modification Date:
2026-01-01 @ 11:53 AM
Study NCT ID:
NCT05303792
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-04-02
First Post:
2022-03-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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
Sponsor:
Alliance for Clinical Trials in Oncology
Organization:
Study Overview
Official Title:
A Randomized Phase II Study Comparing Inotuzumab Plus Chemotherapy Versus Standard Chemotherapy in Older Adults With Philadelphia-Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial compares the combination of inotuzumab ozogamicin and chemotherapy to the usual chemotherapy 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. Giving inotuzumab ozogamicin with chemotherapy may help shrink the cancer and stop it from returning.
Detailed Description:
PRIMARY OBJECTIVE:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-01735 | REGISTRY | NCI Clinical Trial Reporting Program | View | |
| U10CA180821 | NIH | None | https://reporter.nih.gov/quic… | View |