A Phase 1 Trial of Brentuximab Vedotin Plus Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-Cell Lymphomas
Overview
- Phase
- Phase 1
- Intervention
- Brentuximab Vedotin
- Conditions
- CD30-Positive Neoplastic Cells Present
- Sponsor
- City of Hope Medical Center
- Locations
- 1
- Primary Endpoint
- Dose limiting toxicity (DLT) assessed per CTCAE v4.0
- Status
- Withdrawn
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase I trial studies the side effects and best dose of lenalidomide when given together with brentuximab vedotin in treating patients with T-cell lymphomas 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 lymphomas.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD)/Recommended Phase 2 dose (RP2D) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory cutaneous T-cell lymphoma (CTCL). II. Assess safety and tolerability of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL. SECONDARY OBJECTIVES: I. Estimate the rate of objective global response that lasts at least 4 months (ORR4) , complete response (CR) rate, progression-free survival (PFS) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL. II. Estimate the rate and duration of clinically meaningful reduction in pruritus (CMRP). III. Correlate response to baseline CD30 levels in tissue samples. TERTIARY OBJECTIVES: I. Estimate the response endpoints incorporating Lugano response criteria for patients with PET+ disease. II. Explore temporal gene expression profile in skin/ blood samples that may predict response to combination therapy. OUTLINE: This is a dose-escalation study of lenalidomide. Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then up to 12 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented informed consent of the participant and/or legally authorized representative
- •Registered into mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program
- •Women of childbearing potential: adhere to scheduled pregnancy testing as required in the Revlimid REMS program
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Histologically confirmed cutaneous T-cell non-Hodgkin lymphoma (CTCL) per World Health Organization (WHO) classification 2016 including, mycosis fungoides (MF) or Sezary syndrome (SS); phase 1 : \>= stage IIB OR \>= stage IB-IIA folliculotropic/transformed MF; expansion cohort: \>= stage IB
- •MF/SS stage of disease according to TNMB classification
- •SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria
- •For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that been recommended by the International Society for Cutaneous Lymphomas (ISCL) should be used
- •Relapsed/refractory disease
- •Failed \>= 2 prior systemic therapies
Exclusion Criteria
- •Stem cell transplantation
- •Monoclonal antibody within 28 days prior to day 1 of protocol therapy
- •Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating day 1 of protocol therapy
- •Any skin-directed therapy within 14 days prior to day 1 of protocol therapy
- •Any radiation therapy within 21 days prior to day 1 of protocol therapy
- •Immunosuppressive medication within 14 days prior to day 1 of protocol therapy; the following are exceptions to this criterion:
- •Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) and are on stable dose for at least 28 days
- •Systemic corticosteroids at physiologic doses of \< 10 mg/day of prednisone or equivalent
- •Live, attenuated vaccine within 30 days prior to day 1 of protocol therapy
- •Disease free of prior malignancies for \>= 5 years with the exception of:
Arms & Interventions
Treatment (brentuximab vedotin, lenalidomide)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 17 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 days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
Treatment (brentuximab vedotin, lenalidomide)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Dose limiting toxicity (DLT) assessed per CTCAE v4.0
Time Frame: Up to 21 days
Secondary Outcomes
- Rate of objective global response defined as proportion of patients achieving complete response (CR)/partial response (PR) that lasts at least 4 months(At 4 months)
- Complete response defined as proportion of patients achieving CR according to Olsen criteria(Up to 1 year)
- Progression free survival (PFS) according to Olsen criteria(From start of protocol treatment to first observation of disease relapse/ progression or death from any cause, whichever occurs first, assessed up to 1 year)
- CD30 expression assessed by lymph node and/or skin biopsies via immunochemistry(Baseline)
- Change in pruritus visual analogue scale (VAS)(Up to 1 year)