A Phase 1/2 Study of Lenalidomide in Combination With Bendamustine in Relapsed and Primary Refractory Hodgkin Lymphoma (LEBEN)
Management of patients with recurring Hodgkin lymphoma (HL) after stem cell transplantation failure represents a typical unmet medical need prompting active development and validation of new agents and treatment strategies. The LEBEN protocol combines two agents, lenalidomide and bendamustine, framing different targets on both tumor and microenvironmental cells of HL. These agents, while showing a low risk of overlapping extrahematologic toxicities, may hit the proliferation machinery of H-RS cells and/or their progenitors, synergistically inhibit tumor-related angiogenesis and interfere on cytokine-mediate circuitries operating in the microenvironment to support tumor cell survival.
A weekly schedule of bendamustine, at 60 mg/m2, is combined with the continuous administration of increasing dose of lenalidomide (10, 15, 20 e 25 mg dose levels in a 28-day cycle). Such schedule of Bendamustine is aimed at enhancing the antiangiogenic and immunomodulatory activity of continuous Lenalidomide, as studies have shown that low and protracted doses of alkylators induce a decrease in microvascular density of tumor tissues and inhibit mobilization and viability of circulating endothelial progenitors.
The Bayesian phase 1/2 dose finding method of Thall and Cook was employed. This method chooses doses based-on both response and toxicity, and accounts for the trade-off between these two outcomes.
Recurrent Adult Hodgkin Lymphoma
Other: Bio-specimen Retention
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1/2 Study of Lenalidomide in Combination With Bendamustine (LEBEN) in Relapsed and Primary Refractory Hodgkin Lymphoma|
- Dose finding, as best trade-off between toxicity and efficacy according to the Bayesian phase I/II dose finding method of Thall and Cook [ Time Frame: Evaluation at day +56, i.g. after two cycles. ] [ Designated as safety issue: Yes ]According to the Bayesian phase I/II dose finding method of Thall and Cook,a target efficacy-toxicity trade-off contour has been constructed by fitting a curve to target values of pE (probability ofEfficacy) and pT (probability of Toxicity) of 0.30 and 0.40, respectively and probability cut-offs pE (for Efficacy)and pT (for Toxicity) set at 0.10 and 0.10,respectively.The area underneath the target contour has desirable πE, πT pairs. Up to 36 patients can be treated in cohorts of size 3. The 'best' dose is defined as that giving the largest response-toxicity trade-off.
- AE/SAE rate at completion of treatment [ Time Frame: After course 6. i.g. about 6 months ] [ Designated as safety issue: Yes ]
- Overall Rate Response [ Time Frame: After 2, 4 and 6 cycles ] [ Designated as safety issue: No ]
- Event Free Survival [ Time Frame: From the time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason ] [ Designated as safety issue: No ]
- Time to Progression [ Time Frame: From entry until documented lymphoma progression or death as a result of lymphoma. ] [ Designated as safety issue: No ]
- Response Duration [ Time Frame: From the time when criteria for response (i.g. CR or PR) are met, for which the event is the first documentation of relapse or progression. ] [ Designated as safety issue: No ]
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
|Experimental: lenalidomide plus bendamustine||
10, 15, 20 or 25 mg orally per cohort day 1-28 in a 28 days cycle
Other Names:Drug: Bendamustine
intravenous on days 1, 8 and 15 of each 28-days cycle at fixed dose of 60 mg/m2, as a 30-60 min i.v. infusion
Other Names:Other: Bio-specimen Retention
Samples with DNA and without DNA
Please refer to this study by its ClinicalTrials.gov identifier: NCT01412307
|Contact: Gaetano Corazzelli, MD||+39 firstname.lastname@example.org|
|Contact: Mariangela Saggese, PharmaD||+39 email@example.com|
|Hematology Oncology and Stem Cell Transplantation Unit , IRCCS Fondazione "G.Pascale"||Recruiting|
|Naples, Italy, 80131|
|Principal Investigator:||Antonio Pinto, MD||Hematology Oncology and Stem Cell Transplantation Unit , IRCCS Fondazione "G.Pascale" - Naples, Italy|
|Principal Investigator:||Gaetano Corazzelli, MD||Hematology Oncology and Stem Cell Transplantation Unit , IRCCS Fondazione "G.Pascale" - Naples, Italy|