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

NCT ID: NCT01822509

Last Updated: 2021-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

71 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-16

Study Completion Date

2021-06-10

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Allogeneic Hematopoietic Stem Cell Transplant Recipient Myeloproliferative Neoplasm Recurrent Acute Lymphoblastic Leukemia Recurrent Acute Myeloid Leukemia Recurrent Chronic Lymphocytic Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Recurrent Hematologic Malignancy Recurrent Hodgkin Lymphoma Recurrent Myelodysplastic Syndrome Recurrent Non-Hodgkin Lymphoma Recurrent Plasma Cell Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (ipilimumab, nivolumab)

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Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Ipilimumab

Given IV

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew S Davids

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

City of Hope South Pasadena

South Pasadena, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Moffitt Cancer Center-International Plaza

Tampa, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Northside Hospital

Atlanta, Georgia, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Lafayette Family Cancer Center-EMMC

Brewer, Maine, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Charlestown, Massachusetts, United States

Site Status

Countries

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United States

References

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Penter L, Zhang Y, Savell A, Huang T, Cieri N, Thrash EM, Kim-Schulze S, Jhaveri A, Fu J, Ranasinghe S, Li S, Zhang W, Hathaway ES, Nazzaro M, Kim HT, Chen H, Thurin M, Rodig SJ, Severgnini M, Cibulskis C, Gabriel S, Livak KJ, Cutler C, Antin JH, Nikiforow S, Koreth J, Ho VT, Armand P, Ritz J, Streicher H, Neuberg D, Hodi FS, Gnjatic S, Soiffer RJ, Liu XS, Davids MS, Bachireddy P, Wu CJ. Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation. Blood. 2021 Jun 10;137(23):3212-3217. doi: 10.1182/blood.2021010867.

Reference Type DERIVED
PMID: 33720354 (View on PubMed)

Davids MS, Kim HT, Costello C, Herrera AF, Locke FL, Maegawa RO, Savell A, Mazzeo M, Anderson A, Boardman AP, Weber A, Avigan D, Chen YB, Nikiforow S, Ho VT, Cutler C, Alyea EP, Bachireddy P, Wu CJ, Ritz J, Streicher H, Ball ED, Bashey A, Soiffer RJ, Armand P. A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation. Blood. 2020 Jun 11;135(24):2182-2191. doi: 10.1182/blood.2019004710.

Reference Type DERIVED
PMID: 32478814 (View on PubMed)

Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf NR, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, Rodig SJ, Hirakawa M, Severgnini M, Hodi FS, Wu CJ, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Armand P, Streicher H, Ball ED, Ritz J, Bashey A, Soiffer RJ; Leukemia and Lymphoma Society Blood Cancer Research Partnership. Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N Engl J Med. 2016 Jul 14;375(2):143-53. doi: 10.1056/NEJMoa1601202.

Reference Type DERIVED
PMID: 27410923 (View on PubMed)

Other Identifiers

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NCI-2013-00739

Identifier Type: REGISTRY

Identifier Source: secondary_id

12-537

Identifier Type: -

Identifier Source: secondary_id

9204

Identifier Type: OTHER

Identifier Source: secondary_id

9204

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA006516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA183559

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062490

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186709

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2013-00739

Identifier Type: -

Identifier Source: org_study_id

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