Phase II Study of Brentuximab Vedotin in Combination With Pembrolizumab in Patients With Recurrent Systemic Peripheral T-Cell Lymphoma (PTCL)
Overview
- Phase
- Phase 2
- Intervention
- Brentuximab Vedotin
- Conditions
- Recurrent Angioimmunoblastic T-Cell Lymphoma
- Sponsor
- Northwestern University
- Locations
- 1
- Primary Endpoint
- Overall objective response rate (ORR)
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVE: I. To assess the antineoplastic efficacy of brentuximab vedotin in combination with pembrolizumab in previously treated patients with PTCL, as measured by the overall objective response rate (ORR). SECONDARY OBJECTIVES: I. To determine the safety and tolerability of brentuximab vedotin in combination with pembrolizumab. II. To assess efficacy using duration of objective response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS). OUTLINE: Patients receive brentuximab vedotin intravenously (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 stem cell transplantation (SCT). After completion of study treatment, patients are followed up to 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have a histologically-confirmed diagnosis of CD30- positive/expressing peripheral T-cell lymphoma (PTCL). NOTE: All PTCL subtypes are eligible, except for adult T-cell leukemia/Lymphoma (ATLL) and cutaneous T-cell lymphoma (CTCL); ATLL and CTCL are excluded per exclusion criterion below. Examples of eligible subtypes include but are not limited to the following:
- •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.
Exclusion Criteria
- •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
Arms & Interventions
Treatment (brentuximab vedotin, pembrolizumab)
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.
Intervention: Brentuximab Vedotin
Treatment (brentuximab vedotin, pembrolizumab)
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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Overall objective response rate (ORR)
Time Frame: Up to 5 years
Defined as the proportion of evaluable patients who experience an objective response (complete response \[CR\] or partial response \[PR\]) per Lugano Criteria.
Secondary Outcomes
- Incidence of adverse events(30 days after end of treatment)
- Duration of objective response (DOR)(Up to 5 years)
- Progression free survival (PFS)(Up to 5 years)
- Time to response (TTR)(Up to 5 years)
- Overall survival(Up to 5 years)