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

April 1, 2013
April 9, 2014
April 2013
December 2014   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01822509 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Ipilimumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplantation
A Phase I/IB Study of Ipilimumab in Patients With Relapsed Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
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.

Interventions:
  • Biological: ipilimumab
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
Not Provided
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Not Provided
United States
 
NCT01822509
NCI-2013-00739, NCI-2013-00739, 12-537, 9204, U01CA062490, P30CA006516
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Matthew Davids Dana-Farber Cancer Institute
National Cancer Institute (NCI)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP