A phase I/II safety and efficacy trial of a combination of bendamustine, rituximab and lenalidomide (BRL) in patients with relapsed or refractory chronic lymphocytic leukemia

• Conditions: Patients (age 18 or older) with relapsed or refractory chronic lymphocytic leukemia requiring treatment; MedDRA version: 12.1Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemia; MedDRA version: 12.1Level: LLTClassification code 10008977Term: Chronic lymphocytic leukemia recurrent; MedDRA version: 12.1Level: LLTClassification code 10008978Term: Chronic lymphocytic leukemia refractory

• Registration Number: EUCTR2009-012957-39-DE
• Lead Sponsor: niversity of Cologne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-10
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Signed written informed consent.
2.18 years of age or older.
3.Medically fit patients without relevant comorbidity, defined as total CIRS score = 6.
4.WHO performance status of 0-2.
5.Confirmed diagnosis of CLL in need of treatment (Binet C or A/B with active disease) according to the updated IWCLL guidelines (Hallek et al. 2008).
6.Life expectancy > 12 weeks.
7.Relapsed or refractory disease after at least one, but no more than 3 prior regimens. Patients who previously received bendamustine (with or without rituximab) must have had at least a partial response with duration of response of at least six months.
8.Anti-cancer therapy, major surgery, or irradiation was completed > 3 weeks before registration in this study. Patients must have recovered from the acute side effects incurred as a result of previous therapy.
9.Patient is able and willing to receive adequate anticoagulation as specified in this protocol.
10.Adequate liver function as indicated by a total bilirubin, AST, and ALT =2 the institutional ULN value, unless directly attributable to the patient’s tumor.
11.Creatinine clearance >60ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24h-urine collection.
12.ANC > 1500/µl and platelet count > 75.000/µl, unless decrease is due to bone marrow involvement of CLL
13.Negative serological hepatitis B test, negative testing of hepatitis C RNA, negative HIV test within 6 weeks prior to registration.
14.Females of childbearing potential (FOCP) must understand that the study medication has a teratogenic risk and must agree to use, and be able to comply with effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 6 months after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis.

The following are effective methods of contraception
-Implant
-Levonorgestrel-releasing intrauterine system (IUS)
-Medroxyprogesterone acetate depot
-Tubal sterilization
-Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
-Ovulation inhibitory progesterone-only pills (i.e., desogestrel) in combination with another contraceptive method
FOCP must
• agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment.
•agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of conformed tubal sterilization. These pregnancy test should be performed on the day of the study visit or in the 3 days prior to the study visit. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
Male subjects must
•agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study drug therapy if their partner is of childbearing potential and has no contraception
•agree not to donate s

Exclusion Criteria

1.Previously treated with > 3 prior regimens for CLL.
2.Known central nervous system (CNS) involvement of CLL.
3.Patients who have progressed with more aggressive B-cell cancers such as Richter’s syndrome or are diagnosed with B-PLL.
4.History of anaphylaxis following exposure to any of the used study-drugs and/or thalidomide.
5.Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
6.Participation in another clinical trial and/or use of investigational agents or concurrent anti cancer treatment within the last 4 weeks of registration.
7.Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (COPD with hypoxemia), or major organ malfunction that could interfere with the patient’s ability to participate in the study.
8.Pregnant or lactating women.
9.Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
10.Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumor curatively treated by surgery) within the last 5 years before registration.
11.Active bacterial, viral or fungal infection.
12.Medical condition requiring prolonged use of oral corticosteroids (> 1 month).
13.Cerebral dysfunction, legal incapacity.
14.Patients with contraindications according to Summary of Product Characteristics or Investigator’s Brochure.
15.Patients who are employees of the Sponsor (University of Cologne) or the study sites.
16.Persons placed in an institution by legal or official order.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: -dose-limiting toxicity (DLT) and <br>-maximal tolerable dose (MTD) of BRL<br>-Overall response rate (ORR);Secondary Objective: -Response rate (including molecular responses)<br>-Safety assessment<br>-Progression-free survival<br>-Overall survival <br>;Primary end point(s): -dose-limiting toxicity (DLT) and <br>-maximal tolerable dose (MTD) of BRL<br>-Overall response rate (ORR)