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

NCT00840827 | Terminated Phase 2 Results

• 1 other identifier: 0810010063
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic Syndrome

Keywords

stage (IPSS low and INT-1); RBC transfusion-dependent; non-del 5q MDS

Outcome Measures

Primary Outcomes (3)

• 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.

  Efficacy of lenalidomide + CSA will be evaluated as a function of red blood cell transfusion needs improvement (≥ 50% decrease in RBC transfusion requirements after 16 weeks of study treatment).

  16 weeks

• 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.

  Efficacy of lenalidomide + CSA will be evaluated as a function of red blood cell transfusion independence.

  12 months

• 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 by Hemoglobin Change.

  Efficacy of lenalidomide + CSA will be evaluated as a function of change of hemoglobin concentration from baseline to 12 months.

  Baseline and 12 months

Secondary Outcomes (7)

• Safety of Lenalidomide in Combination With CSA in Subjects With Low- or Intermediate-1 Risk MDS Without a Del (5q31-33) Cytogenetic Abnormality by Type of Adverse Events.

  12 months

• Tolerability of Lenalidomide in Combination With CSA in Subjects With Low- or Intermediate-1 Risk MDS Without a Del (5q31-33) Cytogenetic Abnormality by Frequency of Adverse Events.

  12 months

• Tolerability of Lenalidomide in Combination With CSA in Subjects With Low- or Intermediate-1 Risk MDS Without a Del (5q31-33) Cytogenetic Abnormality by Severity of Adverse Events.

  12 months

• Tolerability of Lenalidomide in Combination With CSA in Subjects With Low- or Intermediate-1 Risk MDS Without a Del (5q31-33) Cytogenetic Abnormality by the Relatedness of Adverse Events.

  12 months

• Safety of Lenalidomide in Combination With CSA in Subjects With Low- or Intermediate-1 Risk MDS Without a Del (5q31-33) Cytogenetic Abnormality by Frequency of Adverse Events.

  12 months

Study Arms (1)

all patients

EXPERIMENTAL

Lenalidomide 10mg po daily/ CSA 250mg orally twice daily

Drug: lenalidomide; Drug: cyclosporine A

Interventions

lenalidomide DRUG

Lenalidomide 10mg po daily

Also known as: revlimid

all patients

cyclosporine A DRUG

CSA 250mg orally twice daily

Also known as: Sandimmune

all patients

Eligibility Criteria

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

You may qualify if:

• 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).

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.
• 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)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Lenalidomide; Cyclosporine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

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; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Weill Cornell Medicine

ray2013@med.cornell.edu

212-746-0284

Study Officials

• Eric Feldman, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2009
• First Posted: February 10, 2009
• Study Start: December 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: November 19, 2019
• Results First Posted: November 19, 2019

Record last verified: 2019-11

Locations

US (1)