NCT03851081

Inotuzumab Ozogamicin and Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory CD22+ B-cell Acute Lymphoblastic Leukemia

A Multi-Center, Open-Label Phase 1b/2 Study of Inotuzumab Ozogamicin and Vincristine Sulfate Liposome in Adult Patients With Relapsed/Refractory B Lineage Acute Lymphoblastic Leukemia (B-ALL)

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Roswell Park Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Allogeneic Hematopoietic Stem Cell Transplantation Recipient
• Blasts 5 Percent or More of Bone Marrow Nucleated Cells
• Blasts 5 Percent or More of Peripheral Blood White Cells
• CD22 Positive
• Lymphoblasts 20 Percent or More of Bone Marrow Nucleated Cells
• Lymphoblasts 20 Percent or More of Peripheral Blood White Cells
• Recurrent B Acute Lymphoblastic Leukemia
• Refractory B Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Inotuzumab Ozogamicin	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
DRUG	Vincristine Sulfate Liposome	Given IV

Timeline

• Start date: 2021-01-21
• Primary completion: 2023-01-21
• Completion: 2024-01-21
• First posted: 2019-02-22
• Last updated: 2022-01-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study