Summary

for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
Caitlin Costello

Description

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.

Official Title

A Phase I/IB Study of Ipilimumab or Nivolumab in Patients With Relapsed Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation

Details

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated dose (MTD) of ipilimumab or nivolumab administered to patients with relapsed hematologic malignancies following allogeneic stem cell transplantation. (Phase I) II. To characterize the toxicity of ipilimumab or nivolumab administered at the MTD in this patient population. (Phase Ib)

SECONDARY OBJECTIVES:

  1. To assess response rate. II. To assess progression free and overall survival.

TERTIARY OBJECTIVES:

  1. To assess the phenotypic and functional effects of ipilimumab or nivolumab on immune cells.

OUTLINE: This is a dose-escalation study.

INDUCTION PHASE: Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 8 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive ipilimumab IV over 90 minutes. Treatment repeats every 12 weeks beginning at course 5 (24 weeks after the first dose of ipilimumab) for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving clinical benefit will have the option to continue with ongoing maintenance dosing every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Treatment repeats every 14 days for up to a total of 60 weeks (including Induction) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Keywords

Hematopoietic Cell Transplantation Recipient Myelodysplastic Syndrome Myeloproliferative Neoplasm Previously Treated Myelodysplastic Syndrome Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Chronic Lymphocytic Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Recurrent Hodgkin Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent Plasma Cell Myeloma Lymphoma Syndrome Leukemia Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Lymphoma, Non-Hodgkin Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Myeloid Hodgkin Disease Leukemia, Myelogenous, Chronic, BCR-ABL Positive Myeloproliferative Disorders Multiple Myeloma Neoplasms, Plasma Cell Nivolumab Antibodies, Monoclonal Ipilimumab Laboratory Biomarker Analysis

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 =< 2
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless due to Gilbert's disease or disease-related hemolysis, then =< 3.0 x ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])=< 3.0 x institutional ULN
  • Creatinine =< 1.5 x institutional ULN
  • Prednisone dose =< 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

You CAN'T join if...

  • 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 or active 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

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • City of Hope Comprehensive Cancer Center accepting new patients
    Duarte California 91010 United States
  • UCLA / Jonsson Comprehensive Cancer Center withdrawn
    Los Angeles California 90095 United States

Details

Status
accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT01822509
Phase
Phase 1
Lead Scientist
Caitlin Costello
Study Type
Interventional
Last Updated
May 23, 2018