Non Hodgkin Lymphoma Clinical Trial

Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant

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. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

View Full Description

Full Description

PRIMARY OBJECTIVES:

I. 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:

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

EXPLORATORY OBJECTIVE:

I. 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 cycles 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 cycles 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 cycle 5 (24 weeks after the first dose of ipilimumab) for up to 4 cycles 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.

View Eligibility Criteria

Eligibility Criteria

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 =< 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

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 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 because ipilimumab and nivolumab are immunomodulatory agents with the potential for teratogenic or abortifacient effects; the effects of ipilimumab and nivolumab on the developing human fetus are unknown; for this reason and because immunomodulatory agents are known to be teratogenic, 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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

71

Study ID:

NCT01822509

Recruitment Status:

Completed

Sponsor:

National Cancer Institute (NCI)

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 12 Locations for this study

See Locations Near You

City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States
UC San Diego Moores Cancer Center
La Jolla California, 92093, United States
City of Hope South Pasadena
South Pasadena California, 91030, United States
Colorado Blood Cancer Institute
Denver Colorado, 80218, United States
Moffitt Cancer Center-International Plaza
Tampa Florida, 33607, United States
Moffitt Cancer Center
Tampa Florida, 33612, United States
Northside Hospital
Atlanta Georgia, 30342, United States
Eastern Maine Medical Center
Bangor Maine, 04401, United States
Lafayette Family Cancer Center-EMMC
Brewer Maine, 04412, United States
Massachusetts General Hospital Cancer Center
Boston Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Massachusetts General Hospital
Charlestown Massachusetts, 02129, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

71

Study ID:

NCT01822509

Recruitment Status:

Completed

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.

Please confirm you are a US based health care provider:

Yes, I am a health care Provider No, I am not a health care provider