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Revlimid® as Consolidation Treatment Chronic Lymphocytic Leukemia

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.
 
ClinicalTrials.gov Identifier: NCT01600053
Recruitment Status : Terminated (interim analysis showed that the trial will not meet the interim endpoint.)
First Posted : May 16, 2012
Results First Posted : December 15, 2016
Last Update Posted : December 15, 2016
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Thomas Kipps, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE May 9, 2012
First Posted Date  ICMJE May 16, 2012
Results First Submitted Date  ICMJE December 16, 2015
Results First Posted Date  ICMJE December 15, 2016
Last Update Posted Date December 15, 2016
Study Start Date  ICMJE November 2011
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2012)
Eradication of Residual Disease From the Marrow [ Time Frame: From date of first dose until then end of 12 cycles of treatment (12 months) or progression of disease, whichever comes first. ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 14, 2012)
eradication of disease from the marrow [ Time Frame: Response assessments occur following each course of consolidation and at least 2 months after completion of therapy ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2016)
Recording of the Occurrence of Adverse Events [ Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2012)
recording of the occurrence of adverse events and laboratory tests [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Revlimid® as Consolidation Treatment Chronic Lymphocytic Leukemia
Official Title  ICMJE A Phase II Trial of Revlimid® as Consolidation Treatment of Residual Disease in Patients With Chronic Lymphocytic Leukemia (CLL)
Brief Summary The purpose of this study is to determine whether on course (6 cycles) of consolidation therapy with Revlimid can shrink or slow the growth of Chronic Lymphocytic Leukemia (CLL) in the bone marrow.
Detailed Description

CLL is the most prevalent leukemia in the western world and is considered incurable. Standard therapy for CLL is typically in the form of purine analogs, alkylating agents, monoclonal antibodies, or combinations of these drugs. Unfortunately, despite high response rates these treatment strategies are considered palliative and all patients eventually experience disease relapse and with time become less responsive to therapy. Following standard treatment, CLL patients often fail to achieve a complete response, or they have minimal residual disease (MRD) in the marrow and this often correlates with a short time to progression and next therapy.

The National California Institute Working Group and newly updated International Workshop on Chronic Lymphocytic Leukemia Working Group definition of a complete response (CR) in CLL is quite permissive and allows for the persistence of 30% of residual lymphocytes in the marrow. These response criteria were initially developed at a time treatment options for CLL patients were limited and relatively few CRs were obtained. However, therapeutic advances including monoclonal antibodies and stem cell transplant have reduced residual CLL cells to a greater extent than previously possible and necessitated updating of current response criteria to include MRD evaluation and the development of highly sensitive assays that can measure MRD such as multiparametric 4-color flow cytometry, allele-specific PCR, and more convenient investigational assays such as peripheral blood levels of CLLU-1. Regardless, the majority of complete responses achieved following any initial therapy still have detectable residual disease.

Importantly, CLL patients who lack minimal residual disease following treatment consistently demonstrate prolonged progression free survival (PFS) and overall survival (OS) compared with those with persistent MRD. As such, the development of therapeutic strategies that have the potential to eradicate disease after therapy are highly desired. Such consolidation therapies have potential to improve the depth of a remission, prolong PFS, and potentially overall survival in CLL patients. The investigators propose that Revlimid might be one such therapy that can be used as consolidation to eradicate residual disease or improve remissions in patients who have received therapy and that this might lead to a prolonged disease free duration. The investigators hypothesize that Revlimid will be safe and well tolerated in this setting.

The investigators further hypothesize that Revlimid consolidation might be effective in CLL patients at risk of early relapse such as those patients with leukemia cells that use unmutated immunoglobulin heavy chain variable regions. The investigators found that the relative CLLU1 expression level on blood samples mirrored the residual level of CLL cells as determined by 4-color flow cytometry on cells from the aspirated marrow. The investigators hypothesize that monitoring for expression of CLLU1 might provide a reliable means with which to evaluate residual disease in the context of Revlimid consolidation therapy. Previous single agent Revlimid studies have suggested that Revlimid treatment of CLL patients may positively impact immune parameters increasing the relative composition of T-lymphocytes, modulation of cytokines, and can lead to improvement immunoglobulin levels and or the development of leukemia specific antibodies, the investigators hypothesize that similar changes in immune parameters may occur in the context of Revlimid consolidation therapy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: Lenalidomide
Lenalidomide will be taken orally days 1-21 for up to six 28-day cycles (6 cycles = 1 course of Revlimid consolidation). Revlimid will be initiated at 5mg and can be dose escalated at the start of each cycle based on individual patient tolerability to a maximum of 25 mg. The total number of treatment cycles cannot exceed 12 cycles or two courses of six cycles each.
Other Name: Revlimid
Study Arms  ICMJE Experimental: Lenalidomide
Lenalidomide will be taken orally days 1-21 for up to six 28-day cycles
Intervention: Drug: Lenalidomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 1, 2014)
11
Original Estimated Enrollment  ICMJE
 (submitted: May 14, 2012)
24
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of chronic lymphocytic leukemia:
  • Previously treated patients of any age with a diagnosis of CLL with documented residual disease following therapy, but not meeting an indication for treatment based on current guidelines
  • At least 2 months following previous CLL directed therapy
  • ECOG performance status of less than or equal to 2 at study entry
  • Laboratory test results within these ranges:

    • Platelet count greater than or equal to 50 x 109/L
    • CrCl >.60 ml/min
    • Total bilirubin less than or equal to 1.5 mg/dL
    • AST (SGOT) and ALT (SGPT) less than or equal to 2 x ULN
  • Females of childbearing must adhere to strict guidelines and have negative pregnancy test prior to enrollment
  • Understand and voluntarily sign an informed consent form.
  • Age greater than or equal to 18 years at the time of signing the informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Disease free of prior malignancies for greater than or equal to 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ" of the cervix or breast.
  • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin).

Exclusion Criteria:

  • Known Hepatitis B Ag positive, Hepatitis C positive patients.
  • Known HIV positive patients.
  • Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP)
  • Patients with active fungal, bacterial, and/or viral infection
  • Patients with known hypersensitivity to Revlimid or thalidomide
  • Concurrent use of other anti-cancer agents or treatments
  • Patients with history of deep venous thrombus or pulmonary embolism
  • Patients who are at increased risk of thrombosis during treatment with Revlimid including those taking concurrent erythropoietin, darbepoetin or high-dose corticosteroids
  • Inability to provide informed consent.
  • Concurrent malignancy (excluding basal and squamous cell skin cancers).
  • Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking Revlimid).
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral arterial disease or of recent MI whether or not treated with anti-platelet drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01600053
Other Study ID Numbers  ICMJE 101955
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Kipps, University of California, San Diego
Study Sponsor  ICMJE Thomas Kipps
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Principal Investigator: Thomas J. Kipps, M.D., Ph.D. University of California Medical Center
PRS Account University of California, San Diego
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP