Inotuzumab Ozogamicin in Treating Patients with Acute Lymphocytic Leukemia after Transplant

Status: Active

Description

This phase I / II trial studies the side effects and best dose of inotuzumab ozogamicin and how well it works in treating patients with acute lymphocytic leukemia after transplant. Monoclonal antibodies, such as inotuzumab ozogamicin, may interfere with the ability of cancer cells to grow and spread.

Eligibility Criteria

Inclusion Criteria

  • PHASE I: Diagnosis of CD22-positive acute lymphoblastic leukemia
  • PHASE I: Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • PHASE I: Patients who are between T+40 and T+100 after allogeneic transplantation; patients must receive their first dose of inotuzumab at or before T+100
  • PHASE I: Patients who have/are either: * Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation ** Pre- or post-transplant minimal residual disease defined by: *** Any detectable acute lymphocytic leukemia (ALL) (by flow cytometry, cytogenetics, or polymerase chain reaction [PCR] techniques) as per clinical indication * In second or third complete remission at the time of allogeneic transplantation * Treated with reduced intensity regimens * Lymphoid blast crisis of chronic myelogenous leukemia (CML) * Are relapsed or refractory to at least 1 line of chemotherapy * Philadelphia-like ALL
  • PHASE I: Patients who have evidence of donor chimerism after allogeneic transplantation
  • PHASE I: Philadelphia chromosome positive ALL must have failed at least 1 TKI
  • PHASE I: Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • PHASE I: Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • PHASE I: Subjects must have absolute neutrophil count (ANC) > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 20,000 for 7 days
  • PHASE II: Diagnosis of CD22-positive acute lymphoblastic leukemia
  • PHASE II: Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • PHASE II: Patients who are between T+40 and T+100 after allogeneic transplantation
  • PHASE II: Patients who have/are either: * Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation ** Post-Transplant Minimal Residual Disease defined by: *** Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication * In second or third complete remission at the time of allogeneic transplantation * Treated with reduced intensity regimens * Lymphoid blast crisis of CML * Are relapsed or refractory to at least 1 line of chemotherapy * Philadelphia-like ALL
  • PHASE II: Patients who have >= 80% donor chimerism after allogeneic transplantation
  • PHASE II: Philadelphia chromosome positive ALL must have failed at least 1 TKI
  • PHASE II: ECOG performance status =< 2
  • PHASE II: Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • PHASE II: Subjects must have ANC > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 20,000 for 7 days

Exclusion Criteria

  • Creatinine clearance < 30 ml/min
  • Bilirubin >= 2 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) >= 2 X institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 2 X institutional upper limit of normal
  • Graft versus host disease (GVHD) grade III or IV
  • Active acute or chronic GVHD of the liver
  • History of VOD
  • Active malignancy
  • Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding women are excluded from this study
  • Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds

Locations & Contacts

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Contact: Leland L. Metheny
Phone: 216-844-0139
Email: Leland.Metheny@uhhospitals.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To define a post hematopoietic stem cell transplantation maximum tolerated dose of inotuzumab ozogamicin. (Phase I)

II. To define the safety profile of inotuzumab ozogamicin therapy after allogeneic transplant. (Phase II)

III. To determine the rate of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.

II. To determine the incidence of myeloid toxicity and secondary graft failure.

III. To determine if inotuzumab ozogamicin (inotuzumab) at these doses are effective at eradicating minimal residual disease (MRD) in this cohort of patients.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 30 days and at 1 year.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Leland L. Metheny

Trial IDs

Primary ID CASE1916
Secondary IDs NCI-2017-00826
Clinicaltrials.gov ID NCT03104491