- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02631746
Nivolumab in Treating Patients With HTLV-Associated T-Cell Leukemia/Lymphoma
Phase II Trial of Nivolumab for HTLV-Associated Adult T Cell Leukemia/Lymphoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of nivolumab for patients with HTLV-associated adult T-cell leukemia lymphoma (ATLL).
II. To determine the efficacy of nivolumab for patients with HTLV-associated ATLL.
SECONDARY OBJECTIVES:
I. To determine effects of nivolumab on HTLV-1 proviral deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) loads.
II. To determine the effects of nivolumab on anti-HTLV-1 and anti-ATLL immune responses.
III. To determine effects of nivolumab on HTLV-1 integration site clonality.
OUTLINE:
Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 46 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
-
Bethesda, Maryland, United States, 20892
- NCI - Center for Cancer Research
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
New York
-
Bronx, New York, United States, 10461
- Montefiore Medical Center-Einstein Campus
-
Bronx, New York, United States, 10467
- Montefiore Medical Center - Moses Campus
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with any stage of pathologically confirmed cluster of differentiation (CD)3+ acute, lymphoma, chronic, or smoldering subtypes of ATLL
- Documentation of HTLV infection (enzyme linked immunosorbent assay [ELISA]) in individual with confirmation of HTLV-1 infection (by immunoblot or polymerase chain reaction [PCR]) or a consistent clinical picture (including two of the following: 1) CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean or South American birthplace)
- Patients with acute or lymphoma forms must have received at least one cycle of combination chemotherapy (with or without mogamulizumab) or interferon (with or without zidovudine and/or arsenic); individuals with chronic or smoldering acute T-cell lymphoma (ATL) are not required to have had prior treatment or could have received any number of previous courses of therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%)
- Life expectancy > 12 weeks
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation; women should continue birth control for 23 weeks after stopping nivolumab, and men should continue birth control for 31 weeks after stopping nivolumab; should a woman become pregnant or suspect she is pregnant while she or her partner is 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 31 weeks after completion of nivolumab administration
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
- Prior allogeneic transplantation
- 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
- Any condition requiring > 10 mg/d prednisone equivalents
- Current or prior HTLV-1 associated inflammatory diseases, including but not limited to myelopathy, uveitis, arthropathy, pneumonitis, or a Sjogren's disease-like disorder
- Prior treatment with anti-PD-1, anti-programmed death-ligand (PD-L)1, anti-PD-L2 antibody
- Grade 2 or greater toxicity from prior therapy
- Grade 2 or greater diarrhea
- Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded; patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies (other than HTLV-associated arthropathy), and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible; patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
- Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
- Patients who have hepatitis C (both reactive anti-hepatitis C virus [HCV] antibody and detectable HCV RNA) and hepatitis B (hepatitis B surface antigen [HBsAg] positive and anti-hepatitis B core [HBc]-total positive), may be enrolled, provided their total bilirubin: =< 1.5 x institutional upper limit of normal (ULN) AST (SGOT)/ALT (SGPT): =< 2.5 x institutional upper limit of normal
- Patients with concurrent human immunodeficiency virus (HIV) infection may be enrolled if compliant with 3 or more drug anti-retroviral regimen and virus load less than 50 copies/ml and CD4 count greater than 250 cells/ml, and no concurrent opportunistic infection or other malignancy
- Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with nivolumab
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (nivolumab)
Patients receive nivolumab IV over 60 minutes on day 1.
Treatment repeats every 14 days for 46 courses in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Correlative studies
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events of Nivolumab, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time Frame: 1 year
|
Toxicity by grade will be summarized using descriptive statistics.
The incidence of toxicities will be estimated using the binomial proportion and its 90% confidence interval.
|
1 year
|
Tumor Response, Evaluated Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors Guideline (Version 1.1)
Time Frame: 1 year
|
Summarized using descriptive statistics.
Binomial proportions and their 90% confidence intervals will be used to estimate the response rates of therapy.
|
1 year
|
Duration of Response
Time Frame: 1 year
|
Summarized using descriptive statistics.
Binomial proportions and their 90% confidence intervals will be used to estimate the response rates of therapy.
The Kaplan-Meier method will be used to evaluate the response duration.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effects of Treatment
Time Frame: 1 year
|
Analysis of variance methods will be used to evaluate the effects of treatment.
|
1 year
|
Time on the Viral Load Measurements
Time Frame: 1 year
|
Analysis of variance methods will be used to evaluate the effects of treatment and time on the viral load measurements, as well as measurements of viral transcripts.
A proportional hazards analysis with viral load measures as time dependent covariates will be used to evaluate the effects of these measures on duration of response.
|
1 year
|
HTLV-1 Clonality
Time Frame: 1 year
|
Measured from peripheral blood mononuclear cell (PBMC) samples.
|
1 year
|
HTLV-1 Specific Cytotoxic T Lymphocytes (CTLs)
Time Frame: 1 year
|
Measured from PBMC samples.
|
1 year
|
Immune Cell Numbers
Time Frame: 1 year
|
Measured from blood and tissue samples.
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lee Ratner, Duke University - Duke Cancer Institute LAO
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, Lymphoid
- Deltaretrovirus Infections
- Lymphoma
- Leukemia
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- HTLV-I Infections
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- NCI-2015-02126 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- UM1CA186704 (U.S. NIH Grant/Contract)
- 125462
- 9925 (Other Identifier: CTEP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Adult T-Cell Leukemia/Lymphoma
-
National Cancer Institute (NCI)Completed
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedPeripheral T-cell Lymphoma | Anaplastic Large Cell Lymphoma | Angioimmunoblastic T-cell Lymphoma | Adult Nasal Type Extranodal NK/T-cell Lymphoma | Hepatosplenic T-cell Lymphoma | Recurrent Adult Acute Lymphoblastic Leukemia | Recurrent Adult Hodgkin Lymphoma | Recurrent Adult T-cell Leukemia/Lymphoma and other conditionsUnited States
-
National Cancer Institute (NCI)RecruitingAcute Adult T-Cell Leukemia/Lymphoma | Adult T-Cell Leukemia/Lymphoma | Chronic Adult T-Cell Leukemia/Lymphoma | HTLV-1 InfectionUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Acute Myeloid Leukemia | Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Adult Diffuse Large Cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent... and other conditionsUnited States
-
Juan C. Ramos, MDWithdrawnAcute Lymphoblastic Leukemia | Acute Myelogenous Leukemia | Refractory Leukemia | Adult T-Cell Leukemia/Lymphoma | Relapsed LeukemiaUnited States
-
Columbia UniversityCelgene CorporationCompleted
-
UNC Lineberger Comprehensive Cancer CenterSeagen Inc.Active, not recruitingLymphoma | Lymphatic Diseases | Adult T-Cell Leukemia/LymphomaUnited States
-
University of Alabama at BirminghamTerminatedAnaplastic Large Cell Lymphoma | Angioimmunoblastic T-cell Lymphoma | Peripheral T-cell Lymphomas | Adult T-cell Leukemia | Adult T-cell Lymphoma | Peripheral T-cell Lymphoma Unspecified | T/Null Cell Systemic Type | Cutaneous t-Cell Lymphoma With Nodal/Visceral DiseaseUnited States
-
Kyowa Kirin Co., Ltd.CompletedAdult T-Cell Leukemia and Lymphoma (ATL) | Adult Peripheral T-Cell Lymphoma (PTCL)Japan
-
National Cancer Institute (NCI)CompletedPeripheral T-Cell Lymphoma (PTCL) | T-Cell Prolymphocytic Leukemia | Cutaneous T Cell Lymphoma (CTCL) | T-Cell Lymphoma Relapsed | Adult T-Cell Leukemia (ATL)United States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States