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Acute Adult T-Cell Leukemia/LymphomaPhase 2NCT02631746

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

A Phase 2 study testing Laboratory Biomarker Analysis, Nivolumab and Pharmacogenomic Study in people with Acute Adult T-Cell Leukemia/Lymphoma and Adult T-Cell Leukemia/Lymphoma, run by National Cancer Institute (NCI) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Nivolumab and Pharmacogenomic Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
6 sitesUnited States
Study dates
23 Feb 2017to 31 Jul 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • NCI - Center for Cancer Research

    Bethesda, Maryland, 20892

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: Phase II Trial of Nivolumab for HTLV-Associated Adult T Cell Leukemia/Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Laboratory Biomarker Analysis, Nivolumab, Pharmacogenomic Study
Medical subject headings
Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, HTLV-I Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • Pharmacogenomic StudyOther

    Also called PHARMACOGENOMIC

    Correlative studies

Study groups in NCT02631746
Study groupRoleWhat they receive
Treatment (nivolumab)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacogenomic Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 year

  2. 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.

    Measured: 1 year

  3. 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.

    Measured: 1 year

Secondary outcomes (5)

  1. Effects of Treatment

    Analysis of variance methods will be used to evaluate the effects of treatment.

    Measured: 1 year

  2. Time on the Viral Load Measurements

    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.

    Measured: 1 year

  3. HTLV-1 Clonality

    Measured from peripheral blood mononuclear cell (PBMC) samples.

    Measured: 1 year

  4. HTLV-1 Specific Cytotoxic T Lymphocytes (CTLs)

    Measured from PBMC samples.

    Measured: 1 year

  5. Immune Cell Numbers

    Measured from blood and tissue samples.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2015 (estimated)
  2. Study start23 Feb 2017
  3. Primary completion30 Mar 2018
  4. Study completion31 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02631746
Sponsor's protocol ID
NCI-2015-02126
Other IDs
NCI-2015-02126, 125462, 9925, 9925, UM1CA186704
Status last verified
Mar 2025
First submitted
15 Dec 2015
Last updated
14 Mar 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 31467059

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Nivolumab and Pharmacogenomic Study in people with Acute Adult T-Cell Leukemia/Lymphoma and Adult T-Cell Leukemia/Lymphoma, run by National Cancer Institute (NCI) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02631746, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.

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