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. (see Contacts and Locations)
Verified July 2014 by Fondazione Giovanni Pascale
Sponsor:
Information provided by (Responsible Party):
Antonio Pinto, Fondazione Giovanni Pascale
ClinicalTrials.gov Identifier:
NCT01412307
First received: August 3, 2011
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Adult Hodgkin Lymphoma
Drug: Lenalidomide
Drug: Bendamustine
Other: Bio-specimen Retention
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Fondazione Giovanni Pascale:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 36
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)
Arms Assigned Interventions
Experimental: lenalidomide plus bendamustine 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01412307

Contacts
Contact: Gaetano Corazzelli, MD +39 0815903635 g.corazzelli@istitutotumori.na.it
Contact: Mariangela Saggese, PharmaD +39 0815903671 emadata.pascale@tin.it

Locations
Italy
Hematology Oncology and Stem Cell Transplantation Unit , IRCCS Fondazione "G.Pascale" Recruiting
Naples, Italy, 80131
Sponsors and Collaborators
Fondazione Giovanni Pascale
Investigators
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
  More Information

No publications provided

Responsible Party: Antonio Pinto, Director of Hematology Oncology and Stem Cell Transplant Unit at National Tumor Institute 'Fondazione G. Pascale', Naples - Italy, Fondazione Giovanni Pascale
ClinicalTrials.gov Identifier: NCT01412307     History of Changes
Other Study ID Numbers: LEBEN-HL, 2011-002810-35
Study First Received: August 3, 2011
Last Updated: July 21, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Fondazione Giovanni Pascale:
Hodgkin Lymphoma
Lenalidomide
Bendamustine
Salvage therapy
Palliation

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Nitrogen Mustard Compounds
Lenalidomide
Thalidomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 20, 2014