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Trial record 34 of 179 for:    LENALIDOMIDE AND Leukemia

A Safety and Efficacy Trial of a Combination of Bendamustine, Rituximab and Lenalidomide in Patients With Chronic Lymphocytic Leukemia (CLL2P)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01558167
Recruitment Status : Completed
First Posted : March 20, 2012
Last Update Posted : May 15, 2018
Mundipharma Research GmbH & Co KG
Roche Pharma AG
Information provided by (Responsible Party):
German CLL Study Group

Brief Summary:

This is a prospective, multicenter, open label, non-randomized, phase I/II-study to define safety and efficacy of BRL combination in relapsed/refractory patients and to recommend a safe and efficacious dose for future phase II/III study.

Hypothesis: The simultaneous administration of BRL in relapsed CLL is feasible, safe and efficient.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Bendamustine, Rituximab, Lenalidomide Phase 1 Phase 2

Detailed Description:
As too its mechanism of action lenalidomide seems to work rather by immunomodulation than by a direct anti-proliferative activity against CLL cells. Lenalidomide stimulates T- and NK-cells, modulates the tumour microenvironment in CLL and inhibits bone marrow angiogenesis. There is a rationale to combine lenalidomide with the alpha-CD20 mAb rituximab because lenalidomide enhances NK cell mediated antibody dependent cytotoxicity of rituximab treated NHL cells. On the other hand, there is increasing evidence that the combination of chemotherapy (FC) and rituximab results in highest response rates and longest progression-free survival in treatment naive and relapsed CLL. Besides FCR the combination of bendamustine, a hybrid alkylating agent with properties of a purine-analogue, with rituximab (BR) seems to be very active in relapsed and treatment-naive CLL based on results of a phase II trial of the GCLLSG. Preliminary results with lenalidomide showed a promising response rate of 32% including high risk patients. Thus, the combination of BRL could improve the therapeutic activity in high risk CLL by combining two immunomodulatory with a classic cytotoxic principle.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A phaseI/II Safety and Efficacy Trial of a Combination of Bendamustine, Rituximab and Lenalidomide (BRL) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Study Start Date : February 2011
Actual Primary Completion Date : October 2013
Actual Study Completion Date : June 2015

Arm Intervention/treatment
Experimental: Bendamustine, Rituximab,Lenalidomide
Dose modification treatment plan of lenalidomide
Drug: Bendamustine, Rituximab, Lenalidomide

Bendamustine: 50 mg/m2, i.v., day 1+2

Rituximab: Cycle 1: 375 mg/m2, i.v. day 0; Cycle 2-6: 500mg/m2, i.v., day 1


  • Dose level 1: Cycle 1-6: 2,5mg p.o., d1-28
  • Dose level 2: Cycle 1: 2,5mg p.o., d1-28; Cycle 2-6: 5mg p.o., d1-28
  • Dose level 3: Cycle 1: 2,5mg p.o., d1-28; Cycle 2:5mg p.o., d1-28; Cycle 3-6: 10 mg p.o., d1-28
  • Dose level 4: Cycle 1: 2,5mg p.o., d1-28; Cycle 2:5mg p.o., d1-28; Cycle 3: 10 mg p.o.,d1-28, Cycle 4-6: 15 mg p.o.,d1-28
  • Dose level 5: maximal tolerated dose
Other Names:
  • Ribomustine
  • MabThera
  • Revlimid

Primary Outcome Measures :
  1. dose limiting toxicity [ Time Frame: After 28 days of dosing at the respective target dose level of lenalidomide ]

    DLT defined as

    • absolute neutrophil count < 500/µl for 7 consecutive days or more
    • febrile neutropenia
    • platelet count < 20.000/µl
    • grade 4 tumour flare
    • grade 4 non-hematologic toxicity

Secondary Outcome Measures :
  1. Response rate [ Time Frame: up to 4 years ]
    response will be evaluated according to criteria of the CLL-Guidelines on CLL of the IWCLL-working Group.

  2. progression free survival [ Time Frame: up to 4 years ]

    Progression-free survival based on investigator's assessment:

    PFS is defined as the time from registration to the first occurrence of progression, relapse or death from any cause. Disease progression will be assessed by the investigators using the IWCLL criteria.

  3. Overall Survival [ Time Frame: up to 4 years ]
    Overall survival is defined as the time from registration to death.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. CLL therapy, major surgery, or irradiation for CLL was completed > 4 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01558167

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University Hospital of Cologne
Cologne, Germany, 50924
Sponsors and Collaborators
German CLL Study Group
Mundipharma Research GmbH & Co KG
Roche Pharma AG
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Study Chair: Michael Hallek, Prof.Dr. German CLL Study Group
Study Director: Clemens Wendtner, Prof.Dr. German CLL Study Group

Additional Information:
Publications of Results:
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Responsible Party: German CLL Study Group Identifier: NCT01558167     History of Changes
Other Study ID Numbers: CLL2P
2009-012957-39 ( EudraCT Number )
First Posted: March 20, 2012    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by German CLL Study Group:
Dose limiting toxicity of Lenalidomide
Chronic lymphocytic leukemia
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action