Phase 2 Single-Arm, Open-Label Study of Nivolumab in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Mayo Clinic
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Response Rate for Participants Who Achieve a CR or PR [CT-based Response]
Overview
Brief Summary
This phase II trial studies how well nivolumab works in treating patients with peripheral T-cell lymphoma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the clinical benefit of nivolumab in T-cell lymphomas, as measured by objective response rate (ORR) within 12 cycles according to the Lugano Classification Response Criteria (2014).
SECONDARY OBJECTIVES:
I. To assess safety and tolerability of the regimen in this patient population. II. To assess progression-free survival (PFS). III. To assess duration of response (DOR). IV. To assess overall survival (OS).
TERTIARY OBJECTIVES:
I. To evaluate T-cell/cytokine profile in the peripheral blood - peripheral blood specimens will be used to assess T-cell activation and cytokine up regulation as measures of treatment effect.
II. To evaluate intratumoral biomarkers- intratumoral cell populations and distribution, genetic variability, mutational burden and T-cell activation will be evaluated to identify potential biomarkers that correlate with response to therapy.
III. To assess the potential association between PD-L1/PD-1/PD-L2 expression on tumor and T-cells and/or PD-L1 soluble levels in plasma with clinical efficacy of PD-1 blockade.
OUTLINE:
Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, complete response, or partial response receive nivolumab IV over 60 minutes on day 1 of course 9. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 35 days, 100-120 days, 230-250 days, and 330-390 days.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Relapsed or refractory T-cell lymphoma (TCL) biopsy-proven =\< 6 months prior to registration, including the following subtypes:
- •Peripheral T-cell lymphoma, not otherwise specified
- •Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) negative, primary systemic type
- •Angioimmunoblastic T-cell lymphoma
- •Extranodal natural killer (NK)/T-cell lymphoma, nasal type
- •Adult T-cell lymphoma/leukemia (human T-lymphotropic virus 1 \[HTLV1\]+)
- •Blastic NK-cell lymphoma
- •Enteropathy-associated T-cell lymphoma
- •Hepatosplenic gamma delta T-cell lymphoma
- •Transformed mycosis fungoides
Exclusion Criteria
- •All primary cutaneous T-cell lymphomas
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Active, known or suspected autoimmune disease Note: subjects 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
- •Use of systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications \< 14 days of registration Note: inhaled or topical steroids are permitted; \> 10 mg daily prednisone equivalents are permitted only in adrenal insufficiency in the absence of active autoimmune disease
- •Prohibited treatments and or therapies
- •Autologous stem cell transplant (ASCT) =\< 12 weeks prior to first dose of the study drug
Outcomes
Primary Outcomes
Response Rate for Participants Who Achieve a CR or PR [CT-based Response]
Time Frame: Up to 390 days
The response rate for participants who achieve a CR or PR is defined as the percentage of participants who achieve a CR or PR assessed according to the revised Lugano Classification Response criteria. Complete response (CR): target nodes/nodal masses must regress to \<=1.5 cm in longest transverse diameter (LDi). Partial response (PR): \>= 50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extranodal sites.
Secondary Outcomes
- Response Rate for Participants Who Achieve a CMR or PMR [PET-CT-based Response](Up to 390 days)
- Duration of Response (DOR)(Up to 390 days)
- Overall Survival (OS)(The time from registration to death due to any cause, assessed up to 2 years)
- Progression-Free Survival (PFS)(The time from registration to relapse or death due to any cause, an average of 2 years)
- Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events(Up to 390 days)