Clinical Trial 18950

Cancer Type: Malignant Hematology
Interventions:BMS-936558 (Nivolumab); Nivolumab

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Frederick Locke

Overview

Study Title

A Phase I/Ib Study of Ipilimumab or Nivolumab in Patients with Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation

Summary

This phase I/Ib trial studies the side effects and best dose of ipilimumab or nivolumab in treating patients with cancers of the blood and blood-forming tissues (hematologic cancers) that have returned after a period of improvement (relapsed) after donor stem cell transplant. Monoclonal antibodies, such as ipilimumab and nivolumab, may interfere with the ability of cancer cells to grow and spread.

Objective

Primary Objectives: - Phase I: To determine the maximum tolerated dose (MTD) of ipilimumab or nivolumab administered to patients with relapsed hematologic malignancies following allogeneic stem cell transplantation (alloSCT). - Phase Ib: To characterize the toxicity of ipilimumab or nivolumab administered at the MTD. Secondary Objectives: - To assess response rate. - To assess progression free and overall survival. Exploratory Objectives: - To assess the phenotypic and functional effects of ipilimumab or nivolumab on immune cells.

Inclusion Criteria

  • Histologically or cytologically confirmed hematologic malignancy
  • The following malignancies will be considered eligible if progressive or persistent: Chronic lymphocytic leukemia (CLL); Non-Hodgkin lymphoma (NHL); Hodgkin lymphoma (HL); Multiple myeloma (MM); Acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL]); Myelodysplastic syndrome (MDS); Myeloproliferative neoplasms (MPN); Chronic myeloid leukemia (CML).
  • Life expectancy of greater than 3 months
  • Must have undergone allogeneic hematopoietic stem cell transplantation (HSCT) (regardless of stem cell source)
  • Must have baseline donor T cell chimerism of >= 20%
  • Eastern Cooperative Oncology Group (ECOG) performance status equal to or less than 2
  • Total bilirubin equal to or less than 1.5 x institutional upper limit of normal (ULN) (unless due to Gilbert's disease or disease-related hemolysis, then equal to or less than 3.0 x ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) equal to or less than 3.0 x institutional ULN
  • Creatinine equal to or less than 1.5 x institutional ULN
  • Prednisone dose equal to or less than 5 mg/day and off all other systemic immunosuppressive medications for at least 4 weeks prior to study entry
  • Ability to understand and the willingness to sign a written informed consent document

  • Exclusion Criteria

  • Participants who have had anti-tumor therapy or other investigational agents within 4 weeks prior to registration (6 weeks for nitrosoureas or mitomycin C), or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to registration
  • Patients with prior history of severe (grade 3 or 4) acute graft-versus-host disease (GVHD)
  • Patients with a history of prior treatment with ipilimumab, anti-programmed cell death protein 1 (PD 1) antibody, or cluster of differentiation (CD)137 agonist therapy are ineligible for the ipilimumab arm, but are eligible for the nivolumab arm
  • Patients who have had donor lymphocyte infusion (DLI) within 8 weeks prior to registration
  • Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis); patients with Hashimoto's thyroiditis are eligible to go on study
  • Patients with known chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded
  • Uncontrolled intercurrent 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 women are excluded from this study; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study or within 23 weeks after the last dose of study drug, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 31 weeks after completion of ipilimumab or nivolumab administration