A Phase II Study of Brentuximab Vedotin and Lenalidomide in Relapsed and Refractory T-Cell Lymphomas
Overview
- Phase
- Phase 2
- Intervention
- Brentuximab Vedotin
- Conditions
- Lymphomatoid Papulosis
- Sponsor
- John Reneau
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Overall response rate
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
This phase II trial studies how well brentuximab vedotin and lenalidomide work in treating patients with stage IB-IVB T-cell lymphoma that have come back or do not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and lenalidomide may work better in treating patients with T-cell lymphoma.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) of the combination of brentuximab vedotin (BV) and lenalidomide in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL)/peripheral T-cell lymphoma (PTCL). SECONDARY OBJECTIVES: I. To estimate the duration of response and 2 year progression-free survival (PFS) and overall survival (OS) associated with the combination of brentuximab vedotin (BV) and lenalidomide in patients with relapsed or refractory CTCL/PTCL. II. To define the qualitative and quantitative toxicities of the combination of brentuximab vedotin (BV) and lenalidomide in patients with relapsed or refractory CTCL/PTCL. TERTIARY OBJECTIVES: I. To correlate between the expression of CD30 in neoplastic cells by immunohistochemistry (IHC) and overall response rate (ORR) of the combination of brentuximab vedotin (BV) and lenalidomide in patients with relapsed or refractory CTCL/PTCL. II. To determine T-cell and natural killer (NK) cell subset numbers, phenotype, and functional status in relapsed or refractory (rel/ref) CTCL/PTCL patients, and whether the combination of brentuximab vedotin and lenalidomide alters these parameters during therapy. III. To determine changes in plasma cytokine levels and other biomarkers in this patient population during therapy with the combination of brentuximab vedotin and lenalidomide. OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and lenalidomide orally (PO) once daily (QD) on day 1-21. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Investigators
John Reneau
Principal Investigator
Ohio State University Comprehensive Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Able to understand and voluntarily sign an informed consent form
- •Able to adhere to the study visit schedule and other protocol requirements
- •Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy
- •(Note: extracorporeal photopheresis will be considered a systemic therapy for this study)
- •Patients with large cell transformation of cutaneous T cell lymphoma are eligible
- •Patients with advanced stage non-mycosis fungoides (MF) CTCL are eligible including, but not limited to, advanced stage lymphomatoid papulosis (LyP) or primary cutaneous anaplastic large cell lymphoma (pcALCL)
- •Patients with systemic T cell lymphoma of any stage and any subtypes; patient must have had at least one standard chemotherapy and measurable disease at the time of enrollment; bidimensional measurable disease of at least 1.5 cm in the greatest transverse diameter as documented by computed tomography (CT) or positron emission tomography (PET)/CT
- •Patients with systemic T cell lymphomas who relapsed after autologous transplant are eligible
- •Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV; patients must be at least 3 months from the last dose of BV
- •CD30 staining is to be performed on fresh biopsy or archival formalin-fixed paraffin-embedded (FFPE) tissue however CD30 positivity is not required for eligibility
Exclusion Criteria
- •Patients with active central nervous system (CNS) involvement with lymphoma are not eligible
- •Patients with pre-existing grade \>= 3 peripheral neuropathy
- •Patients with known human immunodeficiency virus (HIV) infection or are not eligible
- •Patients who had solid organ transplants are not eligible
- •Evidence of active hepatitis B infection, based on positive surface antigen or hepatitis B deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), or active hepatitis C infection; patients who are hepatitis B core antibody positive must take prophylaxis with lamivudine or equivalent and be willing to undergo monthly hepatitis B DNA PCR testing
- •Present or history of progressive multifocal leukoencephalopathy (PML)
- •Prior allogeneic stem cell transplant is not permitted
- •Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction likely to interfere with the delivery, absorption, or metabolism of lenalidomide
- •Patients may take steroids for disease control up to 24 hours prior to study enrollment; topical steroids are allowed for CTCL patients as described in inclusion criteria above
- •Any illness, medical condition or organ system dysfunction which, in the investigator?s opinion, could compromise the subject?s safety, interfere with the absorption or metabolism of lenalidomide, or put the study outcomes at undue risk
Arms & Interventions
Treatment (brentuximab vedotin, lenalidomide)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on day 1-21. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Brentuximab Vedotin
Treatment (brentuximab vedotin, lenalidomide)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on day 1-21. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Treatment (brentuximab vedotin, lenalidomide)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on day 1-21. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Overall response rate
Time Frame: Up to 2 years
the overall response rate (ORR) of the combination of brentuximab vedotin (BV) and lenalidomide in patients with relapsed or refractory CTCL/PTCL
Secondary Outcomes
- Incidence of adverse events according to National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0(Up to 30 days after last day of study treatment)
- Overall survival (OS)(From start of study treatment to date of death due to any cause, assessed up to 2 years)
- Progression free survival (PFS)(From start of study treatment to first documentation of tumor progression (including radiographic and clinical progression) or to death due to any cause, whichever comes first, assessed up to 2 years)