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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Jason Robert Gotlib, Stanford University
ClinicalTrials.gov Identifier:
NCT01034592
First received: December 15, 2009
Last updated: December 13, 2016
Last verified: December 2016
  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
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndromes (MDS)
Drug: Lenalidomide

Study Type: Interventional
Study Design: 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 ]
    The primary efficacy endpoint is red blood cell (RBC) transfusion independence (duration must be ≥ 2 months) based on MDS IWG 2000 criteria. RBC transfusion independence is defined as the continuous absence of the intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period, e.g. days 1 to 56, days 2 to 57, days 3 to 58, etc.


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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Bone Marrow Response [ Time Frame: End of cycle 8 (Day 224) or Early Discontinuation, then every 6 months during Maintenance Phase ]
  • Duration of Response [ Time Frame: Day 56 and end of cycle 8 (Day 224) or Early Discontinuation, then every month during Maintenance Phase ]
  • 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 ]
  • 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) ]

Enrollment: 2
Study Start Date: November 2009
Study Completion Date: December 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide
Subjects will initially receive lenalidomide 2.5 mg. The remaining dosage is dependent on patient's response.
Drug: Lenalidomide
2.5 mg/wk up to 5 mg 3x/wk
Other Names:
  • Revlimid
  • CC-5013

Detailed Description:
This pilot study will utilize an intra-patient dose escalation design. Cycles are 28 days in length. Subjects will receive lenalidomide 2.5 mg weekly during days 1-21 of cycle 1 (dose level 1). If patients do not experience any grade >3 hematologic or non-hematologic toxicity, the dose will be increased to 2.5 mg twice weekly on days 1-21 of cycle 2 (dose level 2). If patients do not experience any grade >3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg twice weekly on days 1-21 of cycle 3 (dose level 3). If patients do not experience any grade >3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg thrice weekly on days 1-21 of cycle 4 (dose level 4). Patients who experience grade >3 hematologic or non-hematologic toxicity at dose level 1 will be discontinued from study. Patients who experience grade >3 hematologic or non-hematologic toxicity at dose level 2, 3, or 4 will have the lenalidomide held and dose reduced according to protocol dose interruption/modification algorithms (section 5.5.3). If at least a minor erythroid response is not achieved at the end of 8 cycles of treatment, patients will be discontinued from study. If a minor or major erythroid response is achieved after completion of 8 cycles of treatment, patients can continue study drug on a maintenance phase until loss of erythroid response (return to baseline hemoglobin or transfusion requirement) or unacceptable toxicity.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Jason Robert Gotlib
Celgene Corporation
Investigators
Principal Investigator: Jason Robert Gotlib Stanford University
  More Information

Responsible Party: Jason Robert Gotlib, Assoc Prof-Med Ctr Line in Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01034592     History of Changes
Other Study ID Numbers: IRB-16822
SU-12082009-4523 ( Other Identifier: Stanford University )
RV-0365 ( Other Identifier: Celgene Corporation )
HEMMDS0022 ( Other Identifier: OnCore )
Study First Received: December 15, 2009
Results First Received: December 13, 2016
Last Updated: December 13, 2016
Individual Participant Data  
Plan to Share IPD: No

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

ClinicalTrials.gov processed this record on March 30, 2017