A Phase 1/2 Study of Lenalidomide in combination with Bendamustine (LEBEN) in relapsed and primary refractory Hodgkin Lymphoma
- Conditions
- relapsed and primary refractory Hodgkin LymphomaMedDRA version: 14.1Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2011-002810-35-IT
- Lead Sponsor
- ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI - FONDAZIONE G. PASCALE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
-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/?L
-platelets >75,000/?L
-total bilirubin < 2.0 mg/dl in the absence of a history of Gilbert's disease (or pattern consistent with Gilbert's); 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
?Treatment with chemotherapy or external radiotherapy within 6 weeks, or monoclonal antibodies within 8 weeks or radio-immunoconiugates 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.
?Controindications 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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the best tolerated and effective dose (dose finding) for oral Lenalidomide among 10, 15, 20 e 25 mg dose levels in a 28-day cycle, as associated to a fixed dose of weekly bendamustine (60 mg/m2 on days 1, 8 and 15), based on the best trade-off between toxicity and efficacy according to the Bayesian phase I/II dose finding method of Thall and Cook in subjects with Recurrent Hodgkin Lymphoma;Secondary Objective: 1. To evaluate the safety profile of lenalidomide in combination with bendamustine in terms of AE/SAE rate<br>2. To evaluate the antitumor activity of lenalidomide in combination with bendamustine in terms of ORR, TTP, PFS and response duration;Primary end point(s): NA;Timepoint(s) of evaluation of this end point: NA
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Overall Response rate (CR+PR)<br>•Time to Progression <br>•Event free Survival <br>•Response duration (see section 11.0);Timepoint(s) of evaluation of this end point: na