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

This study is currently recruiting participants.
Verified April 2014 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: April 9, 2014
Last verified: April 2014
  Purpose

This phase I trial studies the side effects and the best dose of ipilimumab in treating patients with relapsed hematologic malignancies after donor stem cell transplantation. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.


Condition Intervention Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Chronic Myelomonocytic Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Previously Treated Myelodysplastic Syndromes
Progressive Hairy Cell Leukemia, Initial Treatment
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
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:

Drug Information available for: Ipilimumab
Genetic and Rare Diseases Information Center resources: Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Lymphoma, Small Cleaved-cell, Diffuse Multiple Myeloma Chronic Myeloproliferative Disorders Acute Lymphoblastic Leukemia Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma B-cell Lymphomas Juvenile Myelomonocytic Leukemia Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Peripheral T-cell Lymphoma Leukemia, T-cell, Chronic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Large Granular Lymphocyte Leukemia
U.S. FDA Resources

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

Primary Outcome Measures:
  • 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 ]
  • 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 ]

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.

  • Progression-free survival [ 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.

  • Overall survival [ 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.


Estimated Enrollment: 40
Study Start Date: April 2013
Estimated Primary Completion Date: December 2014 (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 week 24 and then at weeks 36, 48, and 60 in the absence of disease progression or unacceptable toxicity.

Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
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.

II. To assess tumor glucose metabolism using whole-body fludeoxyglucose F 18-positron emission tomography (FDG-PET) with optional dual time-point imaging.

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 week 24 and then at weeks 36, 48, and 60 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 (AML, ALL)
    • Myelodysplastic Syndrome (MDS)
    • Myeloproliferative Neoplasms (MPN)
    • Chronic Myeloid Leukemia (CML)
  • Must have undergone allogeneic hematopoietic stem cell transplantation (HSCT) (regardless of stem cell source)
  • Must be less than 3 years after withdrawal of all prophylactic immunosuppression
  • Must have baseline donor T cell chimerism of >= 20%
  • Life expectancy of greater than 3 months
  • 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
  • Must be off all immunosuppressive medications for at least 4 weeks prior to study entry
  • Ability to understand and the willingness to sign a written informed consent document
  • Men and women of all races and ethnic groups are eligible for this trial

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 (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, 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 because of potential effects on immune function and/or drug interactions
  • 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 is an immunomodulatory agent with the potential for teratogenic or abortifacient effects
  • 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 administration
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822509

Locations
United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92093-0960
Contact: Caitlin Costello    858-822-6842    ccostello@ucsd.edu   
Principal Investigator: Caitlin Costello         
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         
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         
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, U01CA062490, P30CA006516
Study First Received: April 1, 2013
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Burkitt Lymphoma
Neoplasms
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell
Mycoses
Mycosis Fungoides
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on April 20, 2014