A Phase 1/2 Study of Lenalidomide in Combination With Bendamustine in Relapsed and Primary Refractory Hodgkin Lymphoma (LEBEN)

This study is currently recruiting participants.
Verified August 2011 by Fondazione Giovanni Pascale
Sponsor:
Information provided by:
Fondazione Giovanni Pascale
ClinicalTrials.gov Identifier:
NCT01412307
First received: August 3, 2011
Last updated: August 8, 2011
Last verified: August 2011

August 3, 2011
August 8, 2011
July 2011
March 2013   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01412307 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
A Phase 1/2 Study of Lenalidomide in Combination With Bendamustine in Relapsed and Primary Refractory Hodgkin Lymphoma
A Phase 1/2 Study of Lenalidomide in Combination With Bendamustine (LEBEN) in Relapsed and Primary Refractory Hodgkin Lymphoma

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.

Not Provided
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Adult Hodgkin Lymphoma
  • Drug: Lenalidomide
    10, 15, 20 or 25 mg orally per cohort day 1-28 in a 28 days cycle
    Other Names:
    • CC-5013
    • IMiD-1
    • Revlimid
  • 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:
    • SDX-105
    • Ribomustin
    • Treanda
    • Cytostasan
  • Other: Bio-specimen Retention
    Samples with DNA and without DNA
Not Provided
Corazzelli G, De Filippi R, Capobianco G, Frigeri F, De Rosa V, Iaccarino G, Russo F, Arcamone M, Becchimanzi C, Crisci S, Marcacci G, Amoroso B, Lastoria S, Pinto A. Tumor flare reactions and response to lenalidomide in patients with refractory classic Hodgkin lymphoma. Am J Hematol. 2010 Jan;85(1):87-90. doi: 10.1002/ajh.21571.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
July 2014
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have histologically confirmed classical Hodgkin lymphoma (HL).
  • Patients must have failed an autologous stem cell transplant or be ineligible for high-dose therapy due to chemorefractory disease (as defined as <50% response to standard salvage chemotherapy), age or comorbidity.
  • Patients must have at least one target PET-avid bidimensionally measurable lesion,
  • Age >18 years
  • Life expectancy of greater than 3 months
  • ECOG performance status <2
  • Patients must have adequate organ and marrow function as defined below: absolute neutrophil count >1,000/mL; platelets >75,000/mL; total bilirubin < 2.0 mg/dl in the absence of a history of Gilbert's disease (or pattern consistent with Gilbert's disease); however dose reduction is recommended for Bendamustine in patients with 30 - 70 % tumour involvement of the liver and moderately diminished liver function (serum bilirubin 1.2 - 3.0 mg/dl); AST(SGOT)/ALT(SGPT) <3 X institutional upper limit of normal; creatinine within normal institutional limits OR creatinine clearance >50 mL/min/1.73 m2
  • Patients must have echocardiogram or gated blood pool scan (MUGA) with an ejection fraction > or = to 50%
  • If patients have a history of malignancy other than cutaneous basal cell or squamous cell carcinoma, they must be disease-free for ~ 5 years at the time of enrolment
  • Patients must accept contraception measures until 4 weeks after the completion of chemotherapy, and up to 6 months for male patients.
  • Women of child-bearing must have a medically supervised negative pregnancy test even if had been using effective contraception.
  • Patients agree not to share study medication with another person and to return all unused study drug to the investigator
  • Patients or their guardians must be capable to understand and must be willing to sign a written informed consent document.

Exclusion Criteria:

  • Treatment with chemotherapy or external radiotherapy within 6 weeks, or monoclonal antibodies within 8 weeks or radioimmunoconjugates in the previous 12 weeks prior to entering the study
  • Treatment with any other investigational agent
  • Parenchymal brain or leptomeningeal HL involvement
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study
  • Known HIV positivity or active infectious hepatitis, type A, B, or C
  • Clinically significant cardiac disease (NYHA Class III or IV)
  • Abnormal QTcF interval prolonged (> 459 msec)
  • Known pregnancy or breastfeeding.
  • Jaundice
  • Yellow fever vaccination
  • Medical illness unrelated to HL, which in the opinion of the attending physician and principal investigator will preclude safe administration of lenalidomide and bendamustine
  • Corticoid treatment different from low dose prednisone or methylprednisone (up to 16 mg), used for B symptoms control.
  • Contraindications for receiving prophylaxis against deep vein thrombosis
  • Thromboembolic disease grade 3-4 in the last 6 months
  • More than one month between staging procedures and the start of the treatment
  • Major surgical procedures less than 30 days before the start of treatment
Both
18 Years and older
No
Contact: Gaetano Corazzelli, MD +39 0815903635 g.corazzelli@istitutotumori.na.it
Contact: Mariangela Saggese, PharmaD +39 0815903671 emadata.pascale@tin.it
Italy
 
NCT01412307
LEBEN-HL, 2011-002810-35
Yes
Antonio Pinto, Hematology Oncology and Stem Cell Transplantation Unit , IRCCS Fondazione "G.Pascale" - Naples, Italy
Fondazione Giovanni Pascale
Not Provided
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
Fondazione Giovanni Pascale
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP