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

Relapsed or Refractory Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase 2, Multi-Center, Randomized, Double-Blinded, Parallel Group Study of the Safety and Efficacy of Different Lenalidomide (REVLIMID®) Dose Regimens in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00963105
• Other study ID #: CC-5013-CLL-009
• Secondary ID: 2009-009836-54
• Status: Completed
• Phase: Phase 2
• Start date: October 19, 2009
• Est. completion date: September 5, 2017

Study information

• Verified date: October 2018
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: September 5, 2017
• Est. primary completion date: September 5, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Relapsed or Refractory Chronic Lymphocytic Leukemia

Intervention

Drug:
• lenalidomide
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

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
France	CHU Sud	Amiens
France	Hopital Avicenne	Bobigny Cedex
France	CHU Grenoble	Grenoble Cedex 09
France	Clinique Victor Hugo	Le Mans
France	Institut Paoli Calmettes	Marseille Cedex 9
France	CHU Montpellier - Hôpital Saint Eloi	Montpellier Cedex 5
France	Hopital Emile Muller	Mulhouse
France	Hopital Pitie Salpetriere	Paris
France	CH Perpignan - Hopital Saint-Jean	Perpignan
France	CHRU - Hopital du Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	Hopital Robert Debre	REIMS cedex
France	CHU Rennes Hematology	Rennes cedex
France	CHRU Hopital Brabois	Vandoeuvre les Nancy
Germany	Charite -Universitätsmedizin Berlin	Berlin
Germany	Universitatsklinikum Essen	Essen
Germany	Ernst-Moritz-Arndt-Universität Greifswald	Greifswald
Germany	Universitatsklinikum Schleswig Holstein	Kiel
Germany	Klinikum der Universitat zu Koln	Köln
Germany	University of Ulm Abteilung Innere Medizin III	Ulm
Italy	Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Ematologia ed Immunologia, Azienda Ospedaliera "Vito Fazzi" di Lecce	Lecce
Italy	I.R.C.C.S. Ospedale San Raffaele	Milano
Italy	Istituto Europeo di Oncologia - IEO	Milano
Italy	Universita degli Studi di Padova	Padova
Italy	Universita' Degli Studi Di Perugia	Perugia
Spain	Hospital Clinic Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Sweden	Karolinska Universitetssjukhuset	Stockholm
United Kingdom	St James's Institute of Oncology	Leeds
United Kingdom	King's College Hospital	London
United Kingdom	St.Bartholomew's Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Northwestern University Medical Center Division of Hematology Oncology	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Cancer and Blood Disease Center	Lecanto	Florida
United States	Long Island Jewish Medical Center CLL Research and Treatment Program	New Hyde Park	New York
United States	Drexel University, College of Medicine, Clinical Research Group	Philadelphia	Pennsylvania
United States	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California
United States	Cancer Center of Central Connecticut	Southington	Connecticut
United States	Stanford University School of Medicine	Stanford	California
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

References & Publications (2)

Bühler A, Wendtner CM, Kipps TJ, Rassenti L, Fraser GA, Michallet AS, Hillmen P, Dürig 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:e404. doi: 10.1038/bcj.2016.9. — View Citation

Wendtner CM, Hallek M, Fraser GA, Michallet AS, Hillmen P, Dürig 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response Rate (ORR)	ORR was defined as the percentage of patients with a complete response (CR), CR with incomplete bone marrow (BM) recovery (CRi) or partial response (PR) during treatment. Response was assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. Per the guidelines, a CR required peripheral blood lymphocytes below 4 x 10^9/L, absence of lymphadenopathy, no hepatomegaly or splenomegaly, absence of disease and blood counts neutrophils >1.5 x 10^9/L, platelets >100 x 10^9/L, hemoglobin (hgb) >11g/dL) and BM at least normocellular for age. CRi = CR with incomplete BM recovery. PR = required at least 2 months from end of treatment, a =50% decrease in peripheral blood lymphocyte count from the pre-treatment value and either a = 50% reduction in lymphadenopathy or =50% reduction of liver enlargement or =50% reduction of spleen enlargement plus neutrophils >1.5 x 10^9/ or =50% increase, platelets >100 x 10^9/L or =50% increase, hgb 11 g/dL.	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.
Secondary	Kaplan-Meier Estimate of Duration of Response	Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression.	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.
Secondary	Time to Response	Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period.	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.
Secondary	Kaplan-Meier Estimate of Time to Progression	Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression.	From randomization until the end of the study; maximum time on study was 91 months.
Secondary	Kaplan-Meier Estimate of Event-Free Survival	Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.	From randomization until the end of the study; maximum time on study was 91 months.
Secondary	Kaplan-Meier Estimate of Progression Free Survival	Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.	From randomization until the end of the study; maximum time on study was 91 months.
Secondary	Kaplan-Meier Estimate of Overall Survival	Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented.	From randomization until the end of the study; maximum time on study was 91 months.