Non-Myeloablative Bone Marrow Transplant for Patients With Sickle Cell Anemia and Other Blood Disorders

• Status: Terminated
• Trial end date: 2018-12-29
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving sirolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by a donor bone marrow transplant works in treating patients with sickle cell anemia and other blood disorders.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antilymphocyte Serum; Cyclophosphamide; Etiracetam; Everolimus; Fludarabine; Fludarabine phosphate; Levetiracetam; Mycophenolate mofetil; Mycophenolic Acid; Sirolimus; Thymoglobulin

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following sickle cell anemias (Hb SS):

• Hb S/β° thalassemia

• Hb S/β+ thalassemia

• Hb SC disease

• Hb SE disease

• Hb SD disease

• Hemoglobin SO-Arab disease

• Hb S/hereditary persistence of fetal hemoglobin

• Meets 1 of the following criteria:

• History of invasive pneumococcal disease

• Stroke or CNS event lasting > 24 hours

• MRI changes indicative of brain parenchymal damage

• Evidence of cerebrovascular disease by magnetic resonance angiography

• Acute chest syndrome requiring exchange transfusion or hospitalization

• Recurrent vaso-occlusive pain crisis (> 2 per year for the last 2 years)

• Stage I or II sickle lung disease

• Sickle retinopathy

• Osteonecrosis

• Red cell alloimmunization (> 2 antibodies) during long-term transfusion

• Constellation of dactylitis in the first year of life AND a baseline hemoglobin < 7 g/dL and leukocytosis (WBC > 13.4/mm^3) in the absence of infection during the second year of life

• Pitted RBC count > 3.5% during the first year of life

• Ineligible for or refused bone marrow transplantation from an HLA-matched sibling donor

• Partially mismatched (at least haploidentical) first-degree relative donor available

• No minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky or Lansky PS 70-100%

• LVEF ≥ 35%

• FEV_1 and forced vital capacity ≥ 40% predicted

• Direct bilirubin < 3.1 mg/dL

• No moderate to severe pulmonary hypertension by ECHO

• No debilitating medical or psychiatric illness that would preclude study participation

• No HIV positivity

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior transfusions from donor

• No immunosuppressive agents, including steroids as antiemetics, within 24 hours after the last dose of post-transplantation cyclophosphamide