Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

NCT00963105 | Completed Phase 2 Results DMC

• 2 other identifiers: CC-5013-CLL-0092009-009836-54
• Study Type: interventional
• Target: 104
• Locations: 8 countries
• Sites: 52

Brief Summary

The purpose of this study is to determine the safety and effectiveness of different dose regimens of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Conditions

Relapsed or Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events

  Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event.

  From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

• Kaplan-Meier Estimate of Duration of Response

  Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

• Time to Response

  Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

• Kaplan-Meier Estimate of Time to Progression

  From randomization until the end of the study; maximum time on study was 91 months.

• Kaplan-Meier Estimate of Event-Free Survival

  From randomization until the end of the study; maximum time on study was 91 months.

Study Arms (3)

Lenalidomide 5 mg

EXPERIMENTAL

Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug

Drug: lenalidomide

Lenalidomide 10 mg

EXPERIMENTAL

Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug

Drug: lenalidomide

Lenalidomide 15 mg

EXPERIMENTAL

Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug

Drug: lenalidomide

Interventions

lenalidomide DRUG

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows: * Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily * Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily * Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity

Lenalidomide 10 mg; Lenalidomide 15 mg; Lenalidomide 5 mg

Eligibility Criteria

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

You may qualify if:

• 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 B-cell CLL
• Must be relapsed or refractory to at least 1 regimen for treatment of CLL. At least one of the prior treatments must have included a purine analog-based or bendamustine-based regimen
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Active infections requiring systemic antibiotics
• Systemic treatment for B-cell CLL within 28 days of initiation of lenalidomide treatment
• Alemtuzumab therapy within 120 days of initiating lenalidomide treatment
• Prior therapy with lenalidomide
• History of grade 4 rash due to prior thalidomide treatment
• Planned autologous or allogeneic bone marrow transplantation
• Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
• Uncontrolled hyperthyroidism or hypothyroidism
• Venous thromboembolism within 12 months
• ≥ Grade 2 neuropathy
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
• Disease transformation \[i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia\]
• Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating lenalidomide therapy

Sponsors & Collaborators

• Celgene: lead

Study Sites (52)

UCSD Moores Cancer Center

La Jolla, California, 92093-0820, United States

Location

Desert Hematology Oncology Medical Group, Inc.

Rancho Mirage, California, 92270, United States

Location

Stanford University School of Medicine

Stanford, California, 94305-5821, United States

Location

Cancer Center of Central Connecticut

Southington, Connecticut, 06489, United States

Location

Cancer and Blood Disease Center

Lecanto, Florida, 34461, United States

Location

Northwestern University Medical Center Division of Hematology Oncology

Chicago, Illinois, 60611-2927, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5149, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Long Island Jewish Medical Center CLL Research and Treatment Program

New Hyde Park, New York, 11042, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27104, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Drexel University, College of Medicine, Clinical Research Group

Philadelphia, Pennsylvania, 19102, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

CHU Sud

Amiens, 80054, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CHU Montpellier - Hôpital Saint Eloi

Montpellier, 34295, France

Location

Hopital Emile Muller

Mulhouse, 68000, France

Location

Hopital Pitie Salpetriere

Paris, 75651, France

Location

CH Perpignan - Hopital Saint-Jean

Perpignan, 66046, France

Location

CHRU - Hopital du Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Hopital Robert Debre

Reims, 51092, France

Location

CHU Rennes Hematology

Rennes, 35033, France

Location

CHRU Hopital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Charite -Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Klinikum der Universitat zu Koln

Cologne, 50924, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Ernst-Moritz-Arndt-Universität Greifswald

Greifswald, 17487, Germany

Location

Universitatsklinikum Schleswig Holstein

Kiel, 24116, Germany

Location

University of Ulm Abteilung Innere Medizin III

Ulm, 89081, Germany

Location

Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Ematologia ed Immunologia, Azienda Ospedaliera "Vito Fazzi" di Lecce

Lecce, 73100, Italy

Location

I.R.C.C.S. Ospedale San Raffaele

Milan, 20132, Italy

Location

Istituto Europeo di Oncologia - IEO

Milan, 20141, Italy

Location

Universita degli Studi di Padova

Padua, 35128, Italy

Location

Universita' Degli Studi Di Perugia

Perugia, 06100, Italy

Location

Hospital Clinic Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Karolinska Universitetssjukhuset

Stockholm, 14186, Sweden

Location

St James's Institute of Oncology

Leeds, LS9 7TF, United Kingdom

Location

St.Bartholomew's Hospital

London, EC1M 6BQ, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Christie Hospital NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• Wendtner CM, Hallek M, Fraser GA, Michallet AS, Hillmen P, Durig J, Kalaycio M, Gribben JG, Stilgenbauer S, Buhler A, Kipps TJ, Purse B, Zhang J, De Bedout S, Mei J, Chanan-Khan A. Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial. Leuk Lymphoma. 2016;57(6):1291-9. doi: 10.3109/10428194.2015.1128540. Epub 2016 Jan 14.

  PMID: 26763349 BACKGROUND

• Buhler A, Wendtner CM, Kipps TJ, Rassenti L, Fraser GA, Michallet AS, Hillmen P, Durig J, Gregory SA, Kalaycio M, Aurran-Schleinitz T, Trentin L, Gribben JG, Chanan-Khan A, Purse B, Zhang J, De Bedout S, Mei J, Hallek M, Stilgenbauer S. Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial. Blood Cancer J. 2016 Mar 11;6(3):e404. doi: 10.1038/bcj.2016.9.

  PMID: 26967821 BACKGROUND

MeSH Terms

Conditions

Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

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

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

1-888-260-1599

Study Officials

• Jeffery Jones, M.D., MPH

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2009
• First Posted: August 21, 2009
• Study Start: October 19, 2009
• Primary Completion: September 5, 2017
• Study Completion: September 5, 2017
• Last Updated: October 31, 2018
• Results First Posted: October 2, 2018

Record last verified: 2018-10

Locations

FR (14); IT (6); US (16); ES (2); DE (6); GB (5); SE (1); CA (2)