Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma

NCT05313243 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2000029793No NIH funding
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm, open label, multicenter study phase 2 study of pembrolizumab and brentuximab in subjects with relapsed/refractory CD30 positive T-cell lymphoma (including peripheral T-cell lymphoma and cutaneous T-cell lymphoma) who have received at least one prior therapy. We hypothesize that this combination is effective and will produce an overall response rate of \~55%. Pembrolizumab and brentuximab will be administered for 16 cycles in subjects with responsive disease. Pembrolizumab will be continued for an additional 19 cycles (total 35 cycles). Response assessments will occur at pre-specified intervals. For the primary endpoint the response assessment after 3 cycles will be taken into consideration. Dose adjustments for specific toxicities with either drug are detailed in the protocol. Based on statistical analysis 32 subjects will need to be accrued to evaluate for disease response based on historical control.

Conditions

T-Cell Lymphoma

Keywords

Relapsed; Refractory; CD30 positive; Peripheral T-cell lymphoma; Cutaneous T-cell lymphoma; Pembrolizumab; Brentuximab

Outcome Measures

Primary Outcomes (1)

• The best overall response with the combination of brentuximab and pembrolizumab.

  As assessed by the Lugano criteria for PTCL(16) and the global response score for CTCL(17)

  3 cycles (63 Days)

Secondary Outcomes (6)

• Occurrence of toxicity

  2 Years

• Progression free survival (PFS)

  2 Years

• Overall survival (OS)

  2 Years

• Time to treatment failure

  2 Years

• Duration of response

  2 Years

Study Arms (1)

Brentuximab vedotin (brentuximab) and pembrolizumab

EXPERIMENTAL

All subjects are scheduled to receive up to 16 cycles of combinatorial treatment with brentuximab + pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy. After receiving 35 total doses of pembrolizumab (i.e. scheduled for 16 doses in the combinatorial setting and 8 doses as monotherapy), a subject's pembrolizumab treatment will be complete.

Drug: Brentuximab vedotin; Drug: Pembrolizumab

Interventions

Brentuximab vedotin DRUG

Brentuximab vedotin is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL.

Also known as: Adcetris

Brentuximab vedotin (brentuximab) and pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer.

Also known as: Keytruda

Brentuximab vedotin (brentuximab) and pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (T-NHL) will be enrolled in this study.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including:
• Peripheral T-cell lymphoma not other specified (PTCL nos)
• Angioimmunoblastic T-cell lymphoma (AITL)
• Anaplastic large-cell lymphoma (ALCL)
• Natural killer (NK)/T-cell lymphoma (nodal or extranodal)
• Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary syndrome
• Transformed T-cell lymphoma
• Enteropathy-associated T-cell lymphoma (EATL);
• Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
• Hepatosplenic T- cell lymphomas.
• Presence of CD30 (\>1%) by IHC on a previous biopsy sample
• Relapsed/refractory disease having failed at least one prior systemic therapy Note: Single agent Brentuximab could have been a prior line of therapy EXCEPT those with ≥ grade 2 side effects leading to treatment discontinuation or those refractory to Brentuximab

You may not qualify if:

• Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Patients with adult T-cell leukemia/ lymphoma (ATLL)
• Has received prior systemic anti-cancer therapy including investigational agents ≤ 4 weeks prior to first dose of study treatment on Cycle 1, Day 1. Could consider shorter interval for kinase inhibitors or other short half-life drugs.
• Note: concurrent use of bexarotene or vorinostat (where the dose has been stable for the 8 weeks prior to initiating therapy on trial) is permitted for CTCL. Concurrent use of topical steroids or therapies for CTCL is allowed.
• Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or to baseline value (i.e. condition prior to initiation of the therapy associated with the AE). Participants with ≤Grade 2 neuropathy as AE may be eligible.
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has active autoimmune disease that has required systemic treatment in the past one year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Sponsors & Collaborators

• Yale University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Yale Smilow Cancer Hospital

New Haven, Connecticut, 06510, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (20)

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MeSH Terms

Conditions

Lymphoma, T-Cell; Recurrence; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous

Interventions

Brentuximab Vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Tarsheen Sethi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Ladd, BS

CONTACT

954-895-0576; stephanie.ladd@yale.edu

Julie Holub

CONTACT

Julie.holub@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MSCI, Assistant Professor of Medicine

Model Details: All subjects are scheduled to receive up to 16 cycles of combinatorial treatment with brentuximab + pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy

Study Record Dates

• First Submitted: March 28, 2022
• First Posted: April 6, 2022
• Study Start: July 10, 2023
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 30, 2028
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

US (2)