Pilot Lenalidomide in Adult Diamond-Blackfan Anemia Patients w/ RBC Transfusion-Dependent Anemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Stanford University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT01034592
First received: December 15, 2009
Last updated: March 21, 2011
Last verified: March 2011
  Purpose

This is a single-center, single arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion dependent adult subjects with Diamond-Blackfan Anemia (DBA).

Primary Objective: To evaluate the erythroid response rate as measured by rate of red blood cell transfusion independence (MDS IWG 2000 Criteria will be applied) Secondary Objective: 1)To evaluate the tolerability and safety profile of lenalidomide in patients with DBA and other inherited marrow failure syndromes 2) To correlate response to lenalidomide with biologic surrogates of DBA including ribosomal protein mutation status, ex vivo erythroid colony growth, and microarray gene expression


Condition Intervention
Anemia
Leukemia
Leukemia, Myelocytic, Acute
Dysmyelopoietic Syndromes
Drug: Lenalidomide

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Lenalidomide in Adult Diamond-Blackfan Anemia Patients With Red Blood Cell Transfusion-Dependent Anemia

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • RBC transfusion independence [ Time Frame: Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • >50% decrease in RBC transfusion requirements [ Time Frame: Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase ] [ Designated as safety issue: Yes ]
  • Change of hemoglobin concentration from baseline [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Neutrophil response [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Platelet response [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Bone marrow response [ Time Frame: End of cycle 8 (Day 224) or Early Discontinuation, then every 6 months during Maintenance Phase ] [ Designated as safety issue: Yes ]
  • Duration of response [ Time Frame: Day 56 and end of cycle 8 (Day 224) or Early Discontinuation, then every month during Maintenance Phase ] [ Designated as safety issue: No ]
  • Safety (type, frequency, severity, and relationship of adverse events to lenalidomide) [ Time Frame: Safety is monitored on a continuous basis throughout the trial period, and for 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
  • Correction of clinical response with ribosomal protein mutation status and ex vivo effects of lenalidomide on marrow erythroid colony growth and microarray gene expression signatures [ Time Frame: Assessment done end of cycle 8 (Day 224) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 11
Study Start Date: November 2009
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lenalidomide
    2.5 mg/wk up to 5 mg 3x/wk
    Other Names:
    • Revlimid
    • CC-5013
  Eligibility

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

Inclusion Criteria:1. Understand and voluntarily sign an informed consent form.

2. Diagnosis of DBA.

3.. Age >=18 years at the time of signing the informed consent form.

4. Able to adhere to the study visit schedule and other protocol requirements.

5. Red blood cell transfusion-dependent with a requirement of at least one unit of RBCs per month for the 2 months prior to study enrollment (e.g. 2 units/8 weeks)

6. If applicable, ongoing therapy with a stable or decreasing dose of prednisone <= 60 mg/d or corticosteroid equivalent, for which there has been no treatment-related improvement in RBC transfusion requirements for at least 2 months prior to study entry

7. ECOG performance status of <= 2 at study entry.

8. Laboratory test results within these ranges:

  • Absolute neutrophil count >= 1500/mm>=
  • Platelet count >= 100,000/mm>=
  • Serum creatinine <= 2.0 mg/dL
  • Direct bilirubin <= 1.5 mg/dL
  • AST (SGOT) and ALT (SGPT) <= 2.5 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 "in-situ" of the cervix or breast.

    9. 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 agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

    10. Able to take aspirin (81 - >=25 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)

Exclusion Criteria:1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).

3. 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.

4. Use of any other experimental drug or therapy (excluding steroids) specifically used for DBA within 28 days of baseline including metoclopramide, leucine, danazol, or other hormonal therapy.

5. Clinically significant anemia due to factors such as iron, B12, folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding.

6. Known hypersensitivity to thalidomide.

7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

8. Any prior use of lenalidomide.

9. Concurrent use of other anti-cancer agents or treatments.

10. Known positive for HIV or infectious hepatitis, type A, B or C.

  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: NCT01034592

Contacts
Contact: Andrea Linder (650) 725-4047 andrea.linder@stanford.edu

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Andrea Linder    650-725-4047    andrea.linder@stanford.edu   
Contact: Cancer Clinical Trials Office    (650) 498-7061      
Principal Investigator: Jason Robert Gotlib         
Sub-Investigator: Bertil Glader         
Sub-Investigator: Elizabeth Price         
Sponsors and Collaborators
Stanford University
Celgene Corporation
Investigators
Principal Investigator: Jason Robert Gotlib Stanford University
  More Information

No publications provided

Responsible Party: Jason Robert Gotlib, Stanford University School of Medicine
ClinicalTrials.gov Identifier: NCT01034592     History of Changes
Other Study ID Numbers: SU-12082009-4523, HEMMDS0022, RV-0365
Study First Received: December 15, 2009
Last Updated: March 21, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Anemia
Anemia, Diamond-Blackfan
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Red-Cell Aplasia, Pure
Bone Marrow Diseases
Genetic Diseases, Inborn
Precancerous Conditions
Lenalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014