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Nivolumab in Treating Patients With HTLV-Associated T-Cell Leukemia/Lymphoma

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02631746
First received: December 15, 2015
Last updated: June 19, 2017
Last verified: June 2017
  Purpose
This phase II trial studies how well nivolumab works in treating patients with human T-cell leukemia virus (HTLV)-associated T-cell leukemia/lymphoma. Nivolumab is an antibody, which is a type of blood protein that tags infected cells and other harmful agents. Nivolumab works against a protein called programmed cell death (PD)-1 and may help the body destroy cancer cells by helping the immune system to keep fighting cancer.

Condition Intervention Phase
Acute Adult T-Cell Leukemia/Lymphoma Adult T-Cell Leukemia/Lymphoma CD3 Positive CD4-Positive Neoplastic Cells Present Chronic Adult T-Cell Leukemia/Lymphoma HTLV-1 Infection Hypercalcemia Lymphomatous Adult T-Cell Leukemia/Lymphoma Recurrent Adult T-Cell Leukemia/Lymphoma Smoldering Adult T-Cell Leukemia/Lymphoma Other: Laboratory Biomarker Analysis Biological: Nivolumab Other: Pharmacogenomic Study Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Trial of Nivolumab for HTLV-Associated Adult T Cell Leukemia/Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Duration of response [ Time Frame: From the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 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.

  • Incidence of adverse events of nivolumab, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 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.

  • Tumor response, evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1) [ Time Frame: Up to 1 year ]
    Summarized using descriptive statistics. Binomial proportions and their 90% confidence intervals will be used to estimate the response rates of therapy.


Secondary Outcome Measures:
  • Effects of treatment [ Time Frame: Up to 1 year ]
    Analysis of variance methods will be used to evaluate the effects of treatment.

  • HTLV-1 clonality [ Time Frame: Up to 1 year ]
    Measured from peripheral blood mononuclear cell (PBMC) samples.

  • HTLV-1 specific cytotoxic T lymphocytes (CTLs) [ Time Frame: Up to 1 year ]
    Measured from PBMC samples.

  • Immune cell numbers [ Time Frame: Up to 1 year ]
    Measured from blood and tissue samples.

  • Time on the viral load measurements [ Time Frame: Up to 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.


Estimated Enrollment: 20
Actual Study Start Date: June 3, 2016
Estimated Study Completion Date: July 31, 2017
Estimated Primary Completion Date: July 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Other: Pharmacogenomic Study
Correlative studies
Other Name: PHARMACOGENOMIC

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT02631746

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Kevin C. Conlon    800-411-1222      
Principal Investigator: Kevin C. Conlon         
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Kevin C. Conlon    800-411-1222      
Principal Investigator: Kevin C. Conlon         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Lee Ratner    800-600-3606    info@siteman.wustl.edu   
Principal Investigator: Lee Ratner         
United States, New York
Montefiore Medical Center - Moses Campus Recruiting
The Bronx, New York, United States, 10467-2490
Contact: Murali Janakiram    718-904-2730    aecc@aecom.yu.edu   
Principal Investigator: Murali Janakiram         
United States, North Carolina
Duke University - Duke Cancer Institute LAO Recruiting
Durham, North Carolina, United States, 27710
Contact: Lee Ratner    314-362-8836    lratner@dom.wustl.edu   
Principal Investigator: Lee Ratner         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Jonathan E. Brammer    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Jonathan E. Brammer         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lee Ratner Duke University - Duke Cancer Institute LAO
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02631746     History of Changes
Other Study ID Numbers: NCI-2015-02126
NCI-2015-02126 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
125462
9925 ( Other Identifier: Duke University - Duke Cancer Institute LAO )
9925 ( Other Identifier: CTEP )
UM1CA186704 ( US NIH Grant/Contract Award Number )
Study First Received: December 15, 2015
Last Updated: June 19, 2017

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Hypercalcemia
HTLV-I Infections
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance
Deltaretrovirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017