A Study of Lenalidomide Maintenance for High-risk Patients With CLL Following First-line Therapy

NCT01556776 | Completed Phase 3 DMC

• 3 other identifiers: CLLM12011-004698-98RV-CLL-GCLLSG-0725
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 2

Brief Summary

CLLM1 is a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that compares the efficacy and safety of oral lenalidomide maintenance therapy to that of placebo maintenance therapy in high-risk subjects with Chronic Lymphocytic Leukemia (CLL) who have achieved at least a partial response (PR) and either:

• MRD levels of ≥ 10-2 or
• MRD levels of ≥ 10-4 - \< 10-2 combined with at least one of the following factors:
• an unmutated IGHV-status
• 17p-deletion or
• TP53 mutation after first line therapy with FCR, FR, BR or FC (in case of of contraindications to receive Rituximab).

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL; High Risk; Maintenance

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) based on independent review committee

  Time from the date of randomization to the date of first documented disease progression (as defined by the iWCLL response criteria, see section 4.11.1.2) or death by any cause, whichever occurs first.

  up to 6 years

Secondary Outcomes (4)

• Progression-free survival (PFS) based on investigator's assessment

  up to 6 years

• Overall survival (OS)

  up to 6 years

• Safety - adverse events (AEs)

  up to 6 years

• Miminimal residual disease (MRD) levels in peripheral blood (PB)

  up to 6 years

Study Arms (2)

Lenalidomide

EXPERIMENTAL

lenalidomide maintenance following firstline treatment with FCR, BR, FR, or FC(if Rituximab is contraindicated)

Drug: lenalidomide

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

lenalidomide DRUG

placebo or lenalidomide 5 mg daily on days 1-28 of the first 28-day cycle. If the 5 mg dose level is well tolerated, escalation to 10 mg daily on days 1-28 of cycle 2-6 is permitted; further escalations starting with the 7th cycle and up to the 12th cycle to 15 mg daily is permitted. If after 12 cycles of treatment subjects still present with MRD levels of ≥ 10-4 in peripheral blood and previous dose levels are well tolerated, starting with the 13th cycle up to progression 20 mg daily is permitted. If after 18 cycles of treatment for subjects still present with MRD.levels of ≥ 10-4 in peripheral blood and previous dose levels are well tolerated, starting with the 19th cycle up to progression 25 mg daily is permitted. 25 mg is the maximal daily dose of lenalidomide

Also known as: Revlimid

Lenalidomide

Placebo DRUG

placebo or lenalidomide 5 mg daily on days 1-28 of the first 28-day cycle. If the 5 mg dose level is well tolerated, escalation to 10 mg daily on days 1-28 of cycle 2-6 is permitted; further escalations starting with the 7th cycle and up to the 12th cycle to 15 mg daily is permitted. If after 12 cycles of treatment subjects still present with MRD levels of ≥ 10-4 in peripheral blood and previous dose levels are well tolerated, starting with the 13th cycle up to progression 20 mg daily is permitted. If after 18 cycles of treatment for subjects still present with MRD.levels of ≥ 10-4 in peripheral blood and previous dose levels are well tolerated, starting with the 19th cycle up to progression 25 mg daily is permitted. 25 mg is the maximal daily dose of lenalidomide

Placebo

Eligibility Criteria

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

You may qualify if:

• Must understand and voluntarily sign an informed consent form.
• Age ≥ 18 years at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Must have a documented diagnosis of CLL (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia1.
• Must have been treated with one of the first line induction therapies: fludarabine/cyclophosphamide, fludarabine/rituximab, fludarabine/cyclophosphamide/rituximab, pentostatin/cyclophosphamide/rituximab or bendamustine/rituximab.
• Must have achieved a response of at least PR ((IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia )following completion (minimum 4 cycles) of first line induction therapy prior to randomization, and have either:
• MRD levels in the peripheral blood at final restaging of ≥10-2 or
• MRD levels in the peripheral blood at final restaging of ≥10-4 - \<10-2 combined with an unmutated IGHV-status or 17p-deletion or TP53 mutation.
• Must have completed last cycle of at least 4 cycles of first-line induction no less than 8 weeks (56 days) and no greater than 20 weeks (140 days) prior to randomization.
• Subjects who completed first-line induction treatment with less than 6 cycles but at least 4 cycles should document reason for early discontinuation.
• Must have an Eastern Cooperative Oncology Group (ECOG see appendix 11.13) performance status score of ≤2.
• Negative serological Hepatitis B test or negative PCR in case of positive serological test without evidence of an active infection, negative testing of Hepatitis C RNA, negative HIV test within 6 weeks prior to randomization.
• Females of childbearing potential (FCBP)† must:
• Have two negative medically supervised pregnancy tests prior to starting of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete and continued sexual abstinence.
• Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, two reliable forms of effective contraception simultaneously to achieve a PEARL-Index \<1 without without interruption (Highly effective methods: Intrauterine device (IUD), Hormonal (birth control pills, injections, implants), Tubal ligation, Partner's vasectomy, Additional effective methods: Male condom, Diaphragm, Cervical Cap). 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.

You may not qualify if:

• A CIRS Score of more than 6 or a single score of 4 for an organ system limiting the ability to receive an intensive treatment
• Active infections requiring systemic antibiotics.
• Systemic infection CTC grade 3 or 4 that has not resolved \> 2 months prior to randomization in spite of adequate anti-infective therapy.
• Autologous or allogeneic bone marrow transplant as first line therapy.
• Pregnant or lactating females.
• Systemic treatment for CLL in the interval between completing the last cycle of first-line induction therapy and randomization.
• Participation in any clinical study or having taken any investigational therapy which would interfere with the study drug for a disease other than CLL within 28 days prior to initiating maintenance therapy.
• Known presence of alcohol and/or drug abuse.
• Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging. Subjects who have signs or symptoms suggestive of leukemic meningitis or a history of leukemic meningitis must have a lumbar puncture procedure performed within two weeks prior to randomization.
• Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ≥5 years. Exceptions include the following:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)

Sponsors & Collaborators

• German CLL Study Group: lead
• Celgene: collaborator

Study Sites (2)

University Hospital Cologne

Cologne, 50924, Germany

Location

German CLL Study Group

Cologne, 50937, Germany

Location

Related Publications (2)

• Fink AM, Bahlo J, Robrecht S, Al-Sawaf O, Aldaoud A, Hebart H, Jentsch-Ullrich K, Dorfel S, Fischer K, Wendtner CM, Nosslinger T, Ghia P, Bosch F, Kater AP, Dohner H, Kneba M, Kreuzer KA, Tausch E, Stilgenbauer S, Ritgen M, Bottcher S, Eichhorst B, Hallek M. Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study. Lancet Haematol. 2017 Oct;4(10):e475-e486. doi: 10.1016/S2352-3026(17)30171-0. Epub 2017 Sep 12.

  PMID: 28916311 RESULT

• Furstenau M, Fink AM, Schilhabel A, Weiss J, Robrecht S, Eckert R, de la Serna J, Crespo M, Coscia M, Vitale C, Bottcher S, Weppner G, Ritgen M, Stilgenbauer S, Tausch E, Fischer K, Hallek M, Eichhorst B, Bruggemann M, Herling CD. B-cell acute lymphoblastic leukemia in patients with chronic lymphocytic leukemia treated with lenalidomide. Blood. 2021 Apr 22;137(16):2267-2271. doi: 10.1182/blood.2020008609. No abstract available.

  PMID: 33512465 RESULT

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Anna Fink, MD

  German CLL Study Group

  STUDY CHAIR

• Barbara Eichhorst, MD

  German CLL Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2012
• First Posted: March 16, 2012
• Study Start: July 20, 2012
• Primary Completion: March 1, 2016
• Study Completion: January 14, 2021
• Last Updated: January 5, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)