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Study of the Efficacy and Safety of Lenalidomide in Combination With Cyclosporine A in Patients With Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00840827
First received: January 21, 2009
Last updated: March 8, 2011
Last verified: March 2011
  Purpose

Lenalidomide has shown significant efficacy in the treatment of anemia associated with both 5q- and non 5q- MDS patients. The mechanism(s) of action of lenalidomide in MDS is still to be determined, but given the differences in response rates seen, it is probable that the mechanism is different for patients with 5q- disease compared to non 5q- patients. T-cell mediated activation of intramedullary apoptosis in patients with early MDS leading to impaired hematopoiesis has been well described. Immunomodulation with agents such as ATG, cyclosporine and thalidomide have demonstrated clear activity in some patients with MDS. Lenalidomide, among its many effects, is a potent immunomodulator, which may contribute to its ability to improve red blood cell counts in patients with MDS. It is possible that this effect could be augmented with the addition of cyclosporine A (CSA), in a similar manner to CSA effects in patients with other bone marrow failure syndromes such as aplastic anemia.

Subjects will be treated with lenalidomide 10 mg PO daily days 1-28 of a 28-day cycle. Cyclosporine A will be started on day 1 of cycle 2 (day 29) at a dose of 5 mg/kg per day given orally in 2 divided doses. Cyclosporine A levels will be assessed weekly and doses will be adjusted to maintain a serum trough level between 100-450 mg/ml. Patients will continue on therapy for minimum of 16 weeks unless toxicity occurs which precludes continuation on therapy, disease progression and/or patient withdrawal of consent. Patients not achieving response after completing 16 weeks of therapy will discontinue treatment. Patients achieving response will continue therapy until disease progression, unacceptable toxicity or loss of response.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: lenalidomide
Drug: cyclosporine A
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Arm, Open-Label Study of the Efficacy and Safety of Lenalidomide in Combination With Cyclosporine A in Patients With Red Blood Cell Transfusion-Dependent Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • To evaluate the efficacy of lenalidomide in combination with cyclosporine A (CSA) to achieve red cell transfusion independence in subjects with low- or intermediate-1 risk IPSS MDS without a del (5q31-33) cytogenetic abnormality. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of lenalidomide in combination with CSA in subjects with low- or intermediate-1 risk MDS without a del (5q31-33) cytogenetic abnormality. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • To assess the immunomodulatory effects of the combination of lenalidomide and CSA in patients with MDS. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2008
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: all patients
Lenalidomide 10mg po daily/ CSA 250mg orally twice daily
Drug: lenalidomide
Lenalidomide 10mg po daily
Other Name: revlimid
Drug: cyclosporine A
CSA 250mg orally twice daily
Other Name: Sandimmune

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form.
  • Age ≥ 18 years at the time of signing the informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Diagnosis of low or intermediate-1 risk IPSS (MDS without an abnormality of chromosome 5 involving a deletion between bands q31 and q33. Red blood cell (RBC) transfusion-dependent anemia as having received ≥ 2 units of RBCs within 8 weeks on the first day of study treatment.
  • ECOG performance status of ≤ 2 at study entry
  • Laboratory test results within the following ranges:

    • Absolute neutrophil count (ANC) >500 x 109/L
    • Platelet count ≥ 50 x 109/L
    • Serum creatinine ≤ 2.0 mg/dL
    • Total bilirubin ≤ 1.5 mg/dL
    • AST (SGOT) and ALT (SGPT) ≤ 2 x ULN
  • Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" 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®.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must also agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
  • Able to take asprin (81 or 325 mg) daily as a prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  • 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.
  • Known hypersensitivity to thalidomide. Prior ≥ grade 3 NCI CTCAE (Version 3.0) allergic reaction/hypersensitivity.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Any prior use of lenalidomide.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known positive for HIV or infectious hepatitis, type A, B, or C.
  • Inability to aspirate bone marrow (dry tap).
  • Proliferative (WBC ≥ 12,000/ul) CMML
  • An abnormality of chromosome 5 involving a deletion between bands q31 and q 33.
  • Any of the following lab abnormalities:

    • Absolute neutrophil count (ANC) <500 cells/mm3 (0.5 x 109/L)
    • Platelet count ≤ 50,000/mm3 (50 x 109/L)
    • Serum creatinine ≥ 2.5 mg/dL (221µmol/L)
    • Serum SGOT/AST or SGPT/ALT ≥ 2.0 x upper limit of normal (ULN)
    • Serum direct bilirubin ≥ 2.0 mg/dL (34µmol/L)
  • Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding (if a marrow aspirate is not evaluable for storage iron, transferring saturation must be ≥ 20% and serum ferritin not less than 50ng/mL).
  • Use of hematopoietic growth factors within 7 days of the first day of study drug treatment.
  • Chronic use (≥2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to ≥ 10mg/day of prednisone) within 28 days of the first study drug treatment.
  • Use of experimental or standard drug (i.e chemotherapeutic, immunosuppressive, cytoprotective agents) for the treatment of MDS within 28 days of the first day of study drug
  • Prior history of malignancy other than MDS except basal cell or squamous cell carcinoma in situ of the cervix or breast, unless the patient has been free of disease for ≥ 5 year.
  • Myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure disease. History of active angina, congestive heart disease, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of uncontrolled ischemia and/or active conduction system abnormalities, or myocardial infarction within 6 months prior to enrollment, acute ischemia, or active conduction system abnormalities.
  • Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
  • History of thromboembolic event within the past 6 months prior to enrollment.
  • Patients who have a hypersensitivity to Sandimmune® (cyclosporine).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00840827

Locations
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Celgene Corporation
Investigators
Principal Investigator: Eric Feldman, MD Weill Medical College of Cornell University
  More Information

Additional Information:
No publications provided

Responsible Party: Eric Feldman, MD, Weill Cornell Medical Colelge
ClinicalTrials.gov Identifier: NCT00840827     History of Changes
Other Study ID Numbers: 0810010063
Study First Received: January 21, 2009
Last Updated: March 8, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
stage (IPSS low and INT-1)
RBC transfusion-dependent
non-del 5q MDS

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Cyclosporine
Cyclosporins
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014