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

Leukemia Clinical Trial

Official title:

A Pilot Study of Lenalidomide in Adult Diamond-Blackfan Anemia Patients With Red Blood Cell Transfusion-Dependent Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01034592
• Other study ID #: SU-12082009-4523
• Secondary ID: HEMMDS0022RV-036
• Status: Recruiting
• Phase: N/A
• First received: December 15, 2009
• Last updated: March 21, 2011
• Start date: November 2009
• Est. completion date: November 2013

Study information

• Verified date: March 2011
• Source: Stanford University
• Contact: Andrea Linder
• Phone: (650) 725-4047
• Email: andrea.linder[@]stanford.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11
• Est. completion date: November 2013
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Diamond-Blackfan
• Dysmyelopoietic Syndromes
• Leukemia
• Leukemia, Myelocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Lenalidomide
2.5 mg/wk up to 5 mg 3x/wk

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RBC transfusion independence		Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase	Yes
Secondary	>50% decrease in RBC transfusion requirements		Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase	Yes
Secondary	Change of hemoglobin concentration from baseline		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	Yes
Secondary	Neutrophil response		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	Yes
Secondary	Platelet response		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	Yes
Secondary	Bone marrow response		End of cycle 8 (Day 224) or Early Discontinuation, then every 6 months during Maintenance Phase	Yes
Secondary	Duration of response		Day 56 and end of cycle 8 (Day 224) or Early Discontinuation, then every month during Maintenance Phase	No
Secondary	Safety (type, frequency, severity, and relationship of adverse events to lenalidomide)		Safety is monitored on a continuous basis throughout the trial period, and for 30 days after last dose of study medication	Yes
Secondary	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		Assessment done end of cycle 8 (Day 224)	Yes