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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01822509
First received: April 1, 2013
Last updated: May 4, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
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
Biological: Ipilimumab
Other: Laboratory Biomarker Analysis
Biological: Nivolumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IB Study of Ipilimumab or Nivolumab in Patients With Relapsed Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of adverse events as assessed by NCI CTCAE version 4.0 (Phase Ib) [ Time Frame: Up to 1 year after completion of study treatment ] [ Designated as safety issue: Yes ]
  • MTD of ipilimumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: At 12 weeks ] [ Designated as safety issue: Yes ]
  • MTD of nivolumab according to the NCI CTCAE version 4.0 (Phase I) [ Time Frame: At 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical response [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summarized by simple descriptive summary statistics delineating complete, partial, and best overall response, stable and progressive disease.

  • Overall survival (OS) [ Time Frame: From the start of treatment to time of death, assessed up to 1 year ] [ Designated as safety issue: No ]
    Using the Kaplan-Meier method. Will be analyzed and reported both for the entire cohort and within each disease group if feasible.

  • Progression-free survival (PFS) [ Time Frame: From start of treatment to time of objective disease progression, assessed up to 1 year ] [ Designated as safety issue: No ]
    Using the Kaplan-Meier method. Will be analyzed and reported both for the entire cohort and within each disease group if feasible.


Other Outcome Measures:
  • Change in cytokine production [ Time Frame: Baseline to up to 1 year ] [ Designated as safety issue: No ]
  • Change in immune cell numbers [ Time Frame: Baseline to up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 113
Study Start Date: April 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ipilimumab, nivolumab)
See Detailed Description.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Detailed 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.

TERTIARY OBJECTIVES:

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 courses in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 60 minutes on day 1. Treatment repeats every 14 days for 6 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 a total of 60 weeks (including Induction) 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 60 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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, 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 4 months after completion of ipilimumab or nivolumab administration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01822509

Locations
United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Caitlin Costello    858-822-6842    ccostello@ucsd.edu   
Principal Investigator: Caitlin Costello         
UCLA / Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Contact: John M. Timmerman    310-794-4820    jtimmerman@mednet.ucla.edu   
Principal Investigator: John M. Timmerman         
University of California San Diego Recruiting
San Diego, California, United States, 92103
Contact: Matthew S. Davids       matthew_davids@dfci.harvard.edu   
Principal Investigator: Matthew S. Davids         
United States, Georgia
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Asad Bashey    404-255-1930    abashey@bmtga.com   
Principal Investigator: Asad Bashey         
United States, Maine
Eastern Maine Medical Center Recruiting
Bangor, Maine, United States, 04401
Contact: Jens Rueter    207-973-7478    jrueter@emhs.org   
Principal Investigator: Jens Rueter         
Maine Center for Cancer Medicine-Scarborough Withdrawn
Scarborough, Maine, United States, 04074
United States, Massachusetts
Dana-Farber/Harvard Cancer Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Matthew S. Davids    617-632-6331    Matthew_Davids@dfci.harvard.edu   
Principal Investigator: Matthew S. Davids         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: David E. Avigan    617-667-9920    davigan@bidmc.harvard.edu   
Principal Investigator: David E. Avigan         
Massachusetts General Hospital Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Yi-Bin A. Chen    617-724-1124    yachen@partners.org   
Principal Investigator: Yi-Bin A. Chen         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Stephen M. Ansell    507-284-0923    ansell.stephen@mayo.edu   
Principal Investigator: Stephen M. Ansell         
United States, Tennessee
Northside Hospital Recruiting
Johnson City, Tennessee, United States, 37601
Contact: Matthew S. Davids       matthew_davids@dfci.harvard.edu   
Principal Investigator: Matthew S. Davids         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Matthew Davids Dana-Farber Cancer Institute
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01822509     History of Changes
Other Study ID Numbers: NCI-2013-00739  NCI-2013-00739  12-537  9204  9204  P30CA006516  U01CA062490  UM1CA186709 
Study First Received: April 1, 2013
Last Updated: May 4, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Precancerous Conditions

ClinicalTrials.gov processed this record on May 04, 2016