A Phase I Trial of Brentuximab Vedotin in Combination With Lenalidomide in Relapsed or Refractory Diffuse Large B-cell Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Brentuximab vedotin
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Sponsor
- Washington University School of Medicine
- Enrollment
- 37
- Locations
- 2
- Primary Endpoint
- Safety as measured by grade and frequency of adverse events
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This Phase I clinical trial studies the side effects and maximum tolerated dose (MTD) of the combination of brentuximab vedotin (BV) and lenalidomide in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Relapsed or refractory de novo or transformed DLBCL disease following at least one prior systemic therapy (for DLBCL).
- •CD30 immunohistochemical staining using the anti-CD30 BerH2 antibody must be available on the most recent biopsy specimen. During dose escalation, patients can be either CD30 positive or CD30 negative. During dose expansion, 15 patients must be CD30 positive and 15 patients must be CD30 negative.
- •Post-ASCT or not a candidate for ASCT. Prior allogeneic stem cell transplant is allowed if patient is off all immunosuppressives and has no evidence of active GVHD.
- •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.
- •Bidimensional measurable disease of at least 1.5 cm in the greatest transverse diameter as documented by CT or PET/CT.
- •At least 18 years of age.
- •ECOG performance status ≤ 2
- •Bone marrow and organ function as defined below:
- •Absolute neutrophil count (ANC) ≥ 1,000/mcl
- •Platelets ≥ 50,000/mcl
Exclusion Criteria
- •Primary mediastinal B-cell lymphoma
- •A history of other primary invasive malignancy that has not been in remission for at least 3 years or a current diagnosis of myelodysplastic syndrome (MDS) or an immature leukemia such as acute myeloid leukemia (AML).
- •Known active cerebral/meningeal lymphoma.
- •Present or history of progressive multifocal leukoencephalopathy (PML).
- •NYHA Class III or IV congestive heart failure.
- •Active CTCAE version 4.03 grade 3 or higher viral, bacterial, or fungal infection.
- •Known to be positive for hepatitis B by surface antigen expression and hepatitis B core antibody.
- •Known to have active hepatitis C infection (positive by polymerase chain reaction) or on antiviral therapy for hepatitis C within 6 months prior to the first doses of brentuximab vedotin and lenalidomide.
- •Known to be positive for HIV.
- •Receiving chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed at least 3 weeks prior to study entry, unless underlying disease is progressing on therapy.
Arms & Interventions
Starting Dose (brentuximab vedotin & lenalidomide)
Brentuximab vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.
Intervention: Brentuximab vedotin
Starting Dose (brentuximab vedotin & lenalidomide)
Brentuximab vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.
Intervention: Lenalidomide
Dose Level 1 (brentuximab vedotin & lenalidomide)
Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.
Intervention: Brentuximab vedotin
Dose Level 1 (brentuximab vedotin & lenalidomide)
Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.
Intervention: Lenalidomide
Dose Level 2 (brentuximab vedotin & lenalidomide)
Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.
Intervention: Brentuximab vedotin
Dose Level 2 (brentuximab vedotin & lenalidomide)
Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Safety as measured by grade and frequency of adverse events
Time Frame: 30 days after completion of treatment
Adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Maximum Tolerated Dose (MTD) as measured by the number of dose-limiting toxicities in each dose level (cohort)
Time Frame: Completion of the first cycle for all participants in dose expansion phase (approximately 12 months)
MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached.
Secondary Outcomes
- Overall response rate(Up to 2 years after discontinuation of treatment)
- Objective response rate as measured by CD30 expression(Up to 2 years after discontinuation of treatment)
- Duration of response(Up to 2 years after discontinuation of treatment)
- Progression-free survival (PFS)(Up to 2 years after discontinuation of treatment)