This phase Ib/II trial studies side effects and best dose of inotuzumab ozogamicin and how well it works when given together with vincristine sulfate liposome in treating patients with CD22 positive (+) B-cell acute lymphoblastic leukemia that has come back or dose not respond to treatment. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22+ cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as vincristine sulfate liposome, 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 and vincristine sulfate liposome together may work better in treating patients with CD22+ B-cell acute lymphoblastic leukemia compared to giving inotuzumab ozogamicin or vincristine sulfate liposome alone.
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of vincristine sulfate liposome (liposomal vincristine) and inotuzumab ozogamicin combination therapy in adult patients with relapsed and/or refractory B lineage acute lymphoblastic leukemia (B-ALL). II. To evaluate the overall response rate (ORR consisting of complete remission \[CR\], morphologic CR with incomplete blood count recovery \[CRi\], of combination therapy with liposomal vincristine and inotuzumab ozogamicin in adult patients with relapsed and/or refractory B lineage acute lymphoblastic leukemia. SECONDARY OBJECTIVES: I. To evaluate the leukemia-free survival (LFS) and overall survival (OS) of patients treated with this combination. II. To evaluate the number of patients able to proceed onto subsequent hematopoietic stem cell transplantation (HSCT) following combination therapy following combination therapy. III. To evaluate the overall incidence of unique toxicities associated with these agents, specifically peripheral neuropathy following vincristine sulfate liposome and veno-occlusive disease of the liver (VOD) following inotuzumab ozogamicin therapy. EXPLORATORY OBJECTIVES: I. To explore minimal residual disease (MRD) as a potential correlative biomarker of response to combination vincristine sulfate liposome and inotuzumab ozogamicin therapy. II. To explore potential biomarkers of response to vincristine sulfate liposome and inotuzumab ozogamicin therapy. III. To perform an analysis of the estimated cost of outpatient administration of vincristine sulfate liposome and inotuzumab ozogamicin. IV. To evaluate quality of life (QOL) of patients with relapsed/refractory B-ALL treated with vincristine sulfate liposome and inotuzumab ozogamicin. OUTLINE: This is a phase Ib, dose-escalation study of inotuzumab ozogamicin followed by a phase II study. INDUCTION/RE-INDUCTION: Patients receive vincristine sulfate liposome intravenously (IV) over 1 hour and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve clinical benefit, defined as stable disease (SD), PR or CR, or CRi after 1-2 cycles, will continue on to maintenance therapy for up to 4-5 cycles. Patients who do not achieve clinical benefit after cycle 1 but do not experience dose-limiting toxicities (DLTs) receive a second cycle of vincristine sulfate liposome and inotuzumab ozogamicin. MAINTENANCE: Patients receive vincristine sulfate liposome IV over 1 hour on days 1 and 15 and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 4-5 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Roswell Park Cancer Institute
Buffalo, New York, United States
Dose-limiting toxicities (DLTs) (Phase Ib)
The maximum dose level will be reached when 1 or fewer DLTs are observed in 6 patients.
Time frame: Up to 28 days
Overall response rate (ORR) (Phase II)
Defined as complete remission (CR), morphologic CR with incomplete blood count recovery (CRi), partial remission (PR), hematological improvement (HI) based on modified International Working Group (IWG) criteria. Response is treated as a dichotomous variable and will be summarized by dose level using frequencies and relative frequencies. The ORR will be estimated using an 80% confidence interval obtained by Jeffrey?s prior method.
Time frame: Up to 12 months after last dose of study treatment
Incidence of adverse events (AEs)
Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4 and defined as the number of patients who received study combination who developed subsequent vascular occlusive disease (VOD) or neurological toxicities. The observed AEs and DLTs will be summarized by dose level and grade using frequencies and relative frequencies. AE and DLT rates will be estimated with 90% confidence intervals obtained using Jeffrey?s prior method.
Time frame: Up to 12 months after last dose of study treatment
Leukemia-free survival (LFS)
Will be based on modified IWG criteria. Will be summarized by dose level using standard Kaplan-Meier methods. Estimates of the median LFS will be obtained with 90% confidence intervals.
Time frame: Time from enrollment until disease progression/recurrence, death due to any cause, or last follow-up, assessed up to 12 months after last dose of study treatment
Overall survival
Will be based on modified IWG criteria. Will be summarized by dose level using standard Kaplan-Meier methods. Estimates of the median OS will be obtained with 90% confidence intervals.
Time frame: Time from enrollment until death due to any cause or last follow-up, assessed up to 12 months after last dose of study treatment
Number of patients who proceed onto subsequent hematopoietic stem cell transplantation (HSCT)
The post-therapy HSCT status will be summarized by dose level using frequencies and relative frequencies. The HSCT rate will be estimated with 90% confidence intervals obtained using Jeffrey?s prior method.
Time frame: Up to 12 months after last dose of study treatment
Number of patients who developed subsequent neurological toxicities and VOD
The VOD and neurological toxicities will be summarized by dose level using frequencies and relative frequencies. The toxicity rates will be estimated with 90% confidence intervals obtained using Jeffrey?s prior method.
Time frame: Up to 12 months after last dose of study treatment
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