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

NCT ID: NCT02631746

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-23
• Study Completion Date: 2019-07-31

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.

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Nivolumab

Intervention Type: BIOLOGICAL

Given IV

Pharmacogenomic Study

Intervention Type: OTHER

Correlative studies

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Nivolumab

Given IV

Intervention Type: BIOLOGICAL

Pharmacogenomic Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

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; PHARMACOGENOMIC

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lee Ratner

Role: PRINCIPAL_INVESTIGATOR

Duke University - Duke Cancer Institute LAO

Locations

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

NCI - Center for Cancer Research

Bethesda, Maryland, United States

Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31467059 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2015-02126

Identifier Type: REGISTRY

Identifier Source: secondary_id

125462

Identifier Type: -

Identifier Source: secondary_id

9925

Identifier Type: OTHER

Identifier Source: secondary_id

9925

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA186704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2015-02126

Identifier Type: -

Identifier Source: org_study_id