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

NCT02631746 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2015-021261254629925UM1CA186704
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Acute Adult T-Cell Leukemia/Lymphoma; Adult T-Cell Leukemia/Lymphoma; Chronic Adult T-Cell Leukemia/Lymphoma; HTLV-1 Infection; Lymphomatous Adult T-Cell Leukemia/Lymphoma; Smoldering Adult T-Cell Leukemia/Lymphoma

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events of Nivolumab, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  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)

  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

  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 Outcomes (5)

• Effects of Treatment

  1 year

• Time on the Viral Load Measurements

  1 year

• HTLV-1 Clonality

  1 year

• HTLV-1 Specific Cytotoxic T Lymphocytes (CTLs)

  1 year

• Immune Cell Numbers

  1 year

Study Arms (1)

Treatment (nivolumab)

EXPERIMENTAL

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; Biological: Nivolumab; Other: Pharmacogenomic Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (nivolumab)

Pharmacogenomic Study OTHER

Correlative studies

Also known as: PHARMACOGENOMIC

Treatment (nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Rauch DA, Conlon KC, Janakiram M, Brammer JE, Harding JC, Ye BH, Zang X, Ren X, Olson S, Cheng X, Miljkovic MD, Sundaramoorthi H, Joseph A, Skidmore ZL, Griffith O, Griffith M, Waldmann TA, Ratner L. Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade. Blood. 2019 Oct 24;134(17):1406-1414. doi: 10.1182/blood.2019002038.

  PMID: 31467059 DERIVED

MeSH Terms

Conditions

Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; HTLV-I Infections

Interventions

Nivolumab; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Deltaretrovirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Christy Arrowood
• Organization: Duke University - Duke Cancer Institute LAO

christy.arrowood@duke.edu

919-613-6130

Study Officials

• Lee Ratner

  Duke University - Duke Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 16, 2015
• Study Start: February 23, 2017
• Primary Completion: March 30, 2018
• Study Completion: July 31, 2019
• Last Updated: March 14, 2025
• Results First Posted: March 1, 2019

Record last verified: 2025-03

Locations

US (6)