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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 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: July 9, 2015
Last verified: July 2015
  Purpose

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


Condition Intervention Phase
Myeloproliferative Neoplasm
Previously Treated Myelodysplastic Syndrome
Progression of Multiple Myeloma or Plasma Cell Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Non-Hodgkin Lymphoma
Recurrent Chronic Lymphocytic Leukemia
Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Recurrent Plasma Cell Myeloma
Biological: Ipilimumab
Other: Laboratory Biomarker Analysis
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 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 ]

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.

  • 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.


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: 40
Study Start Date: April 2013
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ipilimumab)

INDUCTION PHASE: Patients receive ipilimumab IV over 90 minutes on day 1.Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive ipilimumab IV over 90 minutes every 12 weeks beginning at course 5 (24 weeks after the first dose of ipilimumab) in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • IPILIMUMAB
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To assess response rate by simple descriptive summary statistics. II. To assess progression free and overall survival by the Kaplan-Meier method.

TERTIARY OBJECTIVES:

I. To assess the phenotypic and functional effects of ipilimumab 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.

MAINTENANCE PHASE: Patients receive ipilimumab IV over 90 minutes every 12 weeks beginning at course 5 (24 weeks after the first dose of ipilimumab) 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
  • 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
  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         
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Peter A. McSweeney    720-754-4800    Peter.McSweeney@HealthONECares.com   
Principal Investigator: Peter A. McSweeney         
United States, Georgia
Blood and Marrow Transplant Group of Georgia Recruiting
Atlanta, Georgia, United States, 30342
Contact: Asad Bashey    404-255-1930    abashey@bmtga.com   
Principal Investigator: Asad Bashey         
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Asad Bashey    404-255-1930    abashey@bmtga.com   
Principal Investigator: Asad Bashey         
United States, Maine
Maine Center for Cancer Medicine-Scarborough Recruiting
Scarborough, Maine, United States, 04074
Contact: Jacquelyn A. Hedlund    207-396-7600    hedluj@newecs.org   
Principal Investigator: Jacquelyn A. Hedlund         
United States, Massachusetts
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         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Matthew S. Davids    617-632-6331    Matthew_Davids@dfci.harvard.edu   
Principal Investigator: Matthew S. Davids         
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Yi-Bin A. Chen    617-724-1124    yachen@partners.org   
Principal Investigator: Yi-Bin A. Chen         
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         
Sponsors and Collaborators
Investigators
Principal Investigator: Matthew Davids Dana-Farber Cancer Institute
  More Information

No publications provided

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, P30CA006516, U01CA062490, UM1CA186709
Study First Received: April 1, 2013
Last Updated: July 9, 2015
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
Leukemia, Plasma Cell
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

ClinicalTrials.gov processed this record on July 26, 2015