Brentuximab Vedotin and Pembrolizumab in Treating Patients With Recurrent Peripheral T-Cell Lymphoma

NCT04795869 | Withdrawn Phase 2 DMC FDA Drug

• 4 other identifiers: NU 20H02NCI-2021-01232STU00213618P30CA060553
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial studies how well giving brentuximab vedotin together with pembrolizumab in treating patients with peripheral T-cell lymphoma (PTCL) that has come back (recurrent). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Pembrolizumab is an antibody-drug that stimulates body's natural antitumor immune responses. Giving brentuximab vedotin together with pembrolizumab may work better than brentuximab vedotin alone in treating patients with recurrent peripheral T-cell lymphoma.

Conditions

Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Follicular T-Cell Lymphoma; Recurrent Hepatosplenic T-Cell Lymphoma; Recurrent Nodal Peripheral T-Cell Lymphoma With TFH Phenotype; Recurrent Peripheral T-Cell Lymphoma, Not Otherwise Specified; Recurrent Subcutaneous Panniculitis-Like T-Cell Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Follicular T-Cell Lymphoma; Refractory Hepatosplenic T-Cell Lymphoma; Refractory Nodal Peripheral T-Cell Lymphoma With TFH Phenotype; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Subcutaneous Panniculitis-Like T-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall objective response rate (ORR)

  Defined as the proportion of evaluable patients who experience an objective response (complete response \[CR\] or partial response \[PR\]) per Lugano Criteria.

  Up to 5 years

Secondary Outcomes (5)

• Incidence of adverse events

  30 days after end of treatment

• Duration of objective response (DOR)

  Up to 5 years

• Time to response (TTR)

  Up to 5 years

• Progression free survival (PFS)

  Up to 5 years

• Overall survival

  Up to 5 years

Study Arms (1)

Treatment (brentuximab vedotin, pembrolizumab)

EXPERIMENTAL

Patients receive brentuximab vedotin IV over 30 minutes on day 1, and pembrolizumab IV over 30 minutes on day 3 of cycle 1, day 1 of subsequent cycles. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles of treatment, patients may discontinue treatment if they experience disease progression, are eligible for stem cell transplant, or if they elect to not undergo SCT.

Drug: Brentuximab Vedotin; Biological: Pembrolizumab

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Treatment (brentuximab vedotin, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (brentuximab vedotin, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• AITL: Angioimmunoblastic T-cell lymphoma
• EATL: Enteropathy-associated T-cell lymphoma
• ENKTL: Extranodal Natural Killer/T-cell Lymphoma
• FTCL: Follicular T-cell lymphoma
• HSTCL: Hepatosplenic T-cell lymphoma
• PTCL-NOS: Peripheral T-cell lymphoma, not otherwise specified
• PTCL-TFH: Nodal peripheral T-cell lymphoma with T-follicular helper phenotype
• SPTCL: Subcutaneous Panniculitis-like T-cell Lymphoma
• ALCL: Anaplastic Large Cell Lymphoma NOTE: CD30-positivity is defined as \>= 1% of cells expressing CD30 as detected by immunohistochemistry (IHC) and determined by local review.
• Patients must have received at least one prior line of systemic therapy and must have relapsed disease or secondary refractory disease meeting one of the below criteria:
• Disease that relapsed within \> 6 months after completion of frontline therapy; or
• Disease that relapsed within any time after completion of secondary/subsequent lines of therapy; or
• Patients must be \>= 18 years of age
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) \>= 1,000/mcL

You may not qualify if:

• Patients who have received prior systemic anti-cancer therapy (including investigational agents) within 4 weeks prior to registration are not eligible. NOTE: Patients must have recovered from all adverse events due to previous therapies to =\< grade 1 or baseline to be eligible. (Exception: =\< grade 2 alopecia is permitted). NOTE: If a patient underwent a major surgery, he/she must have recovered adequately from the toxicity and/or complications from the surgical intervention prior to starting study treatment
• Patients who have received prior radiotherapy within =\< 2 weeks prior to registration are not eligible. EXCEPTION: A \>= 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system \[CNS\] disease. NOTE: Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
• Patients with adult T-cell leukemia/lymphoma (ATLL) or cutaneous T-cell lymphoma are not eligible
• Patients with a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or with current pneumonitis/interstitial lung disease are not eligible
• Patients with a history of allogeneic stem cell transplant or graft-versus host-disease (GvHD) within =\< 5 years prior to registration are not eligible
• Patients who have received 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 (e.g., CTLA-4, OX40, CD137) are not eligible
• Patients with known, active central nervous system (CNS) metastases and/or carcinomatous meningitis are not eligible. NOTE: Patients with previously treated brain metastases may participate, provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
• Patients with a diagnosis of immunodeficiency or who are receiving systemic steroid therapy or any other form of immunosuppressive therapy within =\< 7 days prior to the first dose of trial treatment are not eligible. EXCEPTIONS: Short term steroid preparation prior to tumor imaging is permitted for prophylaxis (e.g., contrast dye allergy)
• Patients with active autoimmune disease that has required systemic treatment (i.e., with the use of disease modifying agents, corticosteroids or immunosuppressive drugs) within =\< 2 years prior to registration are not eligible. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Patients with a history of progressive multifocal leukoencephalopathy (PML) are not eligible
• Patients with a history of pancreatitis are not eligible
• Patients with pre-existing \>= grade 2 peripheral neuropathy are not eligible
• Patients who have a known, additional, active malignancy that is progressing or that requires active treatment are not eligible. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy and in situ cervical cancer
• Patients with a known human immunodeficiency (HIV) infection or active Bacillus Tuberculosis (TB) are not eligible. NOTE: No testing for HIV or TB is required, unless mandated by a local health authority
• Patients with a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or a known, active Hepatitis C virus infection (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) are not eligible.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator
• Merck Sharp & Dohme LLC: collaborator
• Seagen Inc.: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Immunoblastic Lymphadenopathy; Enteropathy-Associated T-Cell Lymphoma; Lymphoma, T-Cell; Subcutaneous panniculitis-like T-cell lymphoma

Interventions

Brentuximab Vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Lymphadenopathy; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms

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

• Jonathan Moreira, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 12, 2021
• Study Start: March 1, 2020
• Primary Completion: March 15, 2026
• Study Completion (Estimated): March 1, 2029
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (1)