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

NCT01558167 | Completed Phase 1

• 2 other identifiers: CLL2P2009-012957-39
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Dose limiting toxicity of Lenalidomide; Chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (1)

• dose limiting toxicity

  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

  After 28 days of dosing at the respective target dose level of lenalidomide

Secondary Outcomes (3)

• Response rate

  up to 4 years

• progression free survival

  up to 4 years

• Overall Survival

  up to 4 years

Study Arms (1)

Bendamustine, Rituximab,Lenalidomide

EXPERIMENTAL

Dose modification treatment plan of lenalidomide

Drug: Bendamustine, Rituximab, Lenalidomide

Interventions

Bendamustine, Rituximab, Lenalidomide DRUG

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 Lenalidomide: * 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

Also known as: Ribomustine, MabThera, Revlimid

Bendamustine, Rituximab,Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent.
• years of age or older.
• Medically fit patients without relevant comorbidity, defined as total CIRS score ≤ 6.
• WHO performance status of 0-2.
• 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).
• Life expectancy \> 12 weeks.
• 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.
• 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.
• Patient is able and willing to receive adequate anticoagulation as specified in this protocol.
• 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.
• Creatinine clearance \>60ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24h-urine collection.
• ANC \> 1500/µl and platelet count \> 75.000/μl, unless decrease is due to bone marrow involvement of CLL
• Negative serological hepatitis B test, negative testing of hepatitis C RNA, negative HIV test within 6 weeks prior to registration.
• 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.

You may not qualify if:

• Previously treated with \> 3 prior regimens for CLL.
• Known central nervous system (CNS) involvement of CLL.
• Patients who have progressed with more aggressive B-cell cancers such as Richter's syndrome or are diagnosed with B-PLL.
• History of anaphylaxis following exposure to any of the used study-drugs and/or thalidomide.
• Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
• Participation in another clinical trial and/or use of investigational agents or concurrent anti cancer treatment within the last 4 weeks of registration.
• 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.
• Pregnant or lactating women.
• Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
• Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumor curatively treated by surgery) within the last 5 years before registration.
• Active bacterial, viral or fungal infection.
• Medical condition requiring prolonged use of oral corticosteroids (\> 1 month).
• Cerebral dysfunction, legal incapacity.
• Patients with contraindications according to Summary of Product Characteristics or Investigator's Brochure.
• Patients who are employees of the Sponsor (University of Cologne) or the study sites.

Sponsors & Collaborators

• German CLL Study Group: lead
• Mundipharma Research GmbH & Co KG: collaborator
• Roche Pharma AG: collaborator
• Celgene: collaborator

Study Sites (1)

University Hospital of Cologne

Cologne, 50924, Germany

Location

Related Publications (1)

• Maurer C, Pflug N, Bahlo J, Kluth S, Rhein C, Cramer P, Gross-Ophoff C, Langerbeins P, Fink AM, Eichhorst B, Kreuzer KA, Fischer N, Tausch E, Stilgenbauer S, Bottcher S, Dohner H, Kneba M, Dreyling M, Binder M, Hallek M, Wendtner CM, Bergmann M, Fischer K; German CLL Study Group. Bendamustine and rituximab in combination with lenalidomide in patients with chronic lymphocytic leukemia. Eur J Haematol. 2016 Sep;97(3):253-60. doi: 10.1111/ejh.12714. Epub 2016 Feb 9.

  PMID: 26643449 RESULT

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bendamustine Hydrochloride; Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Study Officials

• Michael Hallek, Prof.Dr.

  German CLL Study Group

  STUDY CHAIR

• Clemens Wendtner, Prof.Dr.

  German CLL Study Group

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: March 20, 2012
• Study Start: February 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: June 1, 2015
• Last Updated: May 15, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)