Overview

This trial is active, not recruiting.

Condition acute lymphocytic leukemia
Treatment inotuzumab ozogamicin
Phase phase 1/phase 2
Target CD22
Sponsor Pfizer
Collaborator UCB Pharma
Start date August 2011
End date August 2014
Trial size 72 participants
Trial identifier NCT01363297, 3129K6-1106, B1931010

Summary

The Phase 1 portion of this study will assess the safety, tolerability and efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed or refractory adult acute lymphocytic leukemia (ALL) in order to select the recommended phase 2 dose (RP2D) and schedule. The Phase 2 portion of the study will evaluate the efficacy of inotuzumab ozogamicin as measured by hematologic remission rate (CR + CRi) in patients in second or later salvage status.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
inotuzumab ozogamicin CMC-544
Part 1: Administered intravenously as 2 - 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total dose per cycle 0.8 mg/m^2 to 2.0 mg/m^2. Part 2 Expansion and Part 3 Phase 2: Administered intravenously as 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total initial dose per cycle 1.8 mg/m^2.

Primary Outcomes

Measure
Part 1: Dose-Finding First cycle dose limiting toxicities (DLTs).
time frame: duration of first cycle, approximately 1-56 days from first dose
Part 1: Dose-Finding Preliminary efficacy, including non-progressive disease (PD) after the first cycle.
time frame: duration of first cycle, approximately 28-56 days from first dose
Part 2: Expansion Cohort Hematologic remission [complete response (CR) and complete response with incomplete count recovery (CRi)]
time frame: duration of treatment period, approximately 2-6 months from first dose
Part 3: Phase 2 Hematologic remission [complete response (CR) and complete response with incomplete count recovery (CRi)]
time frame: duration of treatment period, approximately 2-6 months from first dose

Secondary Outcomes

Measure
Hematologic response, including complete response (CR), complete response with incomplete count recovery (CRi) and partial response (PR)
time frame: duration of treatment period, approximately 2-6 months from first dose
Minimal residual disease levels and cytogenetics in subjects achieving hematologic remission (CR + CRi)
time frame: duration of treatment period, approximately 2-6 months from first dose
Number of subjects who undergo stem-cell transplant following treatment with inotuzumab ozogamicin
time frame: duration of long-term follow-up period, up to 2 years from first dose
Duration of response (DoR)
time frame: duration of treatment and long-term follow-up periods, up to 2 years from first dose
Progression-free survival (PFS)
time frame: duration of treatment and long-term follow-up periods, up to 2 years from first dose
Overall survival (OS)
time frame: duration of treatment and long-term follow-up periods, up to 2 years from first dose
Population pharmacokinetic parameters of inotuzumab ozogamicin, including clearance and volume of distribution for the typical subject as well as the individual
time frame: up to 4 cycles, approximately 4 months from the first dose
Pharmacodynamic parameters of inotuzumab ozogamicin, including rate of clearance of CD22-positive B-cells from peripheral blood, and PK/PD relationship
time frame: up to 4 cycles, approximately 4 months from the first dose
Pharmacogenomic parameters including expression of genes related to DNA repair and susceptibility to apoptosis triggered by double-stranded DNA breaks
time frame: duration of first half of cycle 1, approximately 2 weeks from first dose
Duration of remission (DoR1)
time frame: duration of treatment and long-term follow-up periods, up to 2 years from first dose

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Subjects with CD22-positive ALL with either refractory disease (i.e. disease progression or no response while receiving their most recent prior anti-cancer therapy), or relapsed disease (i.e. response to their most recent prior anti-cancer therapy with subsequent relapse). Subjects enrolled in the Phase 2 portion of the study must be due to receive salvage 2 or later therapy. - Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor. - Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential. Exclusion Criteria: - Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia. - Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry. - Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).

Additional Information

Official title An Open-label, Phase 1/2 Study Of Inotuzumab Ozogamicin In Subjects With Relapsed Or Refractory Cd22-positive Acute Lymphocytic Leukemia
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Pfizer.