Dear DBA Patients and Families:

We are pleased to announce the opening of the “Pilot Study of Lenalidomide (Revlimid) in Adult Patients with Red Blood Cell Transfusion-Dependent Anemia” at the Stanford University Medical Center.

The rationale for evaluating lenalidomide in DBA comes from the study of an acquired form of bone marrow failure named myelodysplastic syndrome (MDS).  Although DBA is inherited, and MDS usually develops in older adults, they share several clinical and laboratory features:  poor production of red blood cells often leading to a need for frequent blood transfusions, and a somewhat increased risk of developing acute leukemia.  Iron overload from chronic red blood cell transfusions is a common and serious problem.

Mutations in more than 10 ribosomal proteins have now been identified in greater than 50% of DBA patients and are now implicated as the cause of the disease.  In a very important  report published in Nature in 2008, Dr. Benjamin Ebert and colleagues at Harvard discovered that loss of the gene encoding ribosomal protein S14 was critical to the cause of a form of MDS called 5q- syndrome.  In this subtype of MDS, a region of the long arm of chromosome 5 is missing, and ribosomal protein gene S14 is located in this missing segment.  This was an unexpected and important finding, since it was the first time that a common biologic link was found between DBA and MDS.

In patients with 5q- MDS who depend on red blood cell transfusions, the oral medication lenalidomide (Revlimid) can eliminate the need for transfusions in 70% of subjects.  Given the outstanding red blood cell response rate to lenalidomide in 5q- MDS in which loss of ribosomal protein S14 has emerged as an important discovery, there is a strong reason for investigating lenalidomide in DBA in which ribosomal protein deficiency is also linked to impaired red blood cell production.

The following are some of the basic inclusion and exclusion criteria for this pilot trial:

Inclusion Criteria

  • Age >18 years at the time of signing the informed consent form.
  • 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)
  • 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
  • Laboratory test results within these ranges:
  • Absolute neutrophil count ≥1500/mm³
  • Platelet count ≥ 100,000/mm³
  • Serum creatinine ≤ 2.0 mg/dL
  • Direct bilirubin ≤ 1.5 mg/dL
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x upper limit of normal
  • 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.
  • Females of childbearing potential must have a negative serum or urine pregnancy test.
  • Able to take aspirin (81 – 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion criteria

  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  • 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.
  • Clinically significant anemia due to factors such as iron, B12, folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding.
  • Known hypersensitivity to thalidomide.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known positive for HIV or infectious hepatitis, type A, B or C.

Please refer to the website link: http://www.clinicaltrials.gov and enter the search term “Diamond-Blackfan Anemia and lenalidomide” for full eligibility criteria and additional trial information.

NOTE:  BECAUSE THIS STUDY IS CURRENTLY ONLY BEING CONDUCTED AT STANFORD, WE HAVE FUNDS TO COVER PATIENT TRAVEL EXPENSES. 

CONTACT INFORMATION

Principal Investigator:  Dr. Jason Gotlib, Stanford University School of Medicine

Co-Investigator:  Dr. Bertil Glader, Stanford University School of Medicine

Scientific Co-Investigators:  Dr. Hanna Gazda, Boston Children’s Hospital/Harvard
Dr. Benjamin Ebert, Brigham and Women’s Hospital/Harvard

We appreciate the support and commitment of Drs. Adrianna Vlachos and Jeffrey Lipton and their leadership of the DBA Registry in making this study possible.

Please contact our study nurse, Andrea Linder:

TEL:  650-725-4047
FAX:  650-723-1269
Email: alinder@stanford.edu

Also, feel free to contact Dr. Gotlib by email: jason.gotlib@stanford.edu