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

August 8, 2015 updated by: Antonio Pinto, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Naples, Italy, 80131
        • Hematology Oncology and Stem Cell Transplantation Unit , IRCCS Fondazione "G.Pascale"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Treanda
  • SDX-105
  • Ribomustin
  • Cytostasan
Other: Bio-specimen Retention
Samples with DNA and without DNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
Evaluation at day +56, i.g. after two cycles.

Secondary Outcome Measures

Outcome Measure
Time Frame
AE/SAE rate at completion of treatment
Time Frame: After course 6. i.g. about 6 months
After course 6. i.g. about 6 months
Overall Rate Response
Time Frame: After 2, 4 and 6 cycles
After 2, 4 and 6 cycles
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
From the time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason
Time to Progression
Time Frame: From entry until documented lymphoma progression or death as a result of lymphoma.
From entry until documented lymphoma progression or death as a result of lymphoma.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Nazionale Tumori IRCCS - Fondazione G. 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • http://meetinglibrary.asco.org/content/132091-144

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

July 1, 2015

Study Completion (Anticipated)

July 1, 2016

Study Registration Dates

First Submitted

August 3, 2011

First Submitted That Met QC Criteria

August 8, 2011

First Posted (Estimate)

August 9, 2011

Study Record Updates

Last Update Posted (Estimate)

August 11, 2015

Last Update Submitted That Met QC Criteria

August 8, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LEBEN-HL
  • 2011-002810-35 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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