Pembrolizumab + Brentuximab for T-Cell Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Tarsheen Sethi

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Yale University

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it allows the concurrent use of certain medications like bexarotene or vorinostat for CTCL if the dose has been stable for 8 weeks before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab + Brentuximab for T-Cell Lymphoma?

Research shows that Brentuximab vedotin, one of the drugs in the treatment, has been effective in improving response rates and quality of life in patients with certain types of T-cell lymphomas, such as cutaneous T-cell lymphoma, when compared to standard therapies. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Brentuximab safe for humans?

Brentuximab vedotin has shown an acceptable safety profile in patients with certain types of lymphoma, and Pembrolizumab is generally safe but can rarely cause type 1 diabetes in 0.2% of cases. Both drugs have been studied separately and have demonstrated safety in humans for various conditions. ^{2 3 6 7 8}

What makes the drug Pembrolizumab + Brentuximab unique for T-Cell Lymphoma?

This drug combination is unique because it combines Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells, with Brentuximab vedotin, a targeted therapy that specifically attacks CD30-positive cancer cells, offering a novel approach for treating T-cell lymphomas. ^{3 4 5 7 9}

Research Team

Tarsheen Sethi

Principal Investigator

Yale University

Eligibility Criteria

Adults with a confirmed diagnosis of T-cell Non-Hodgkin lymphoma, including various subtypes like PTCL and CTCL, who have CD30 positive cells and have failed at least one prior therapy. Participants must be over 18, not pregnant or breastfeeding, willing to use contraception, and have good organ function. Exclusions include those with certain other health conditions or treatments that could interfere with the trial.

Inclusion Criteria

I have a lymphoma with a detectable tumor larger than 1.5 cm.

Participant provides written informed consent for the trial

I am fully active or can carry out light work.

Exclusion Criteria

I am currently fighting an infection that needs treatment.

Known psychiatric or substance abuse disorders

History or current evidence of conditions that might interfere with the study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 16 cycles of brentuximab and pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy

35 cycles

Response Assessment

Response assessments occur at pre-specified intervals, with primary response assessment after 3 cycles

63 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Brentuximab vedotin (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The study is testing the combination of Pembrolizumab and Brentuximab Vedotin in patients with relapsed/refractory T-cell lymphoma. It's an open-label phase 2 trial where both drugs are given for up to 16 cycles if effective; Pembrolizumab may continue for a total of 35 cycles. The goal is to see if this combo can achieve around a 65% overall response rate.

Participant Groups

Group I: Brentuximab vedotin (brentuximab) and pembrolizumab Experimental Treatment 2 Interventions

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.

Brentuximab vedotin is already approved in Canada, Japan for the following indications:

Approved in Canada as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma

Approved in Japan as Adcetris for:

• Hodgkin lymphoma
• Anaplastic large cell lymphoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Yale Smilow Cancer Hospital New Haven, CT

Dana Farber Cancer Institute Boston, MA

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1963

Patients Recruited

3,046,000+

Sethi

Lead Sponsor

Trials

2

Patients Recruited

70+

Tarsheen Sethi

Lead Sponsor

Trials

2

Patients Recruited

70+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4096

Patients Recruited

5,232,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. Dummer, R., Prince, HM., Whittaker, S., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Prince, HM., Kim, YH., Horwitz, SM., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Beats Standard Therapies for CTCL. [2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Horwitz, S., O'Connor, OA., Pro, B., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time has come for immunotherapy in PTCL. Bachy, E., Coiffier, B.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. Han, TH., Chen, R., Advani, R., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Kuruvilla, J., Ramchandren, R., Santoro, A., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin therapy for CD30-positive cutaneous T-cell lymphoma: a targeted approach to management. Scarisbrick, JJ.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Brentuximab Beats Standard Therapies for CTCL. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Time has come for immunotherapy in PTCL. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin therapy for CD30-positive cutaneous T-cell lymphoma: a targeted approach to management. [2019]