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

NCT00489281 | Terminated Phase 2 Results

• 4 other identifiers: J0676P30CA006973P01CA015396NA_00002479
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease

Outcome Measures

Primary Outcomes (2)

• Transplant-related Mortality

  Number of participants who died for reasons related to bone marrow transplant.

  Up to one year

• Progression-free Survival

  Percentage of participants who are alive without relapse.

  2 years

Secondary Outcomes (2)

• Donor Chimerism at 30 Days

  30 days

• Donor Chimerism at 1 Year

  1 year

Study Arms (2)

Transplant - 200 cGy

EXPERIMENTAL

Conditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 200. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Allogeneic bone marrow transplant; Radiation: Total body irradiation - 200; Drug: Levetiracetam; Biological: Anti-thymocyte globulin

Transplant - 400 cGy

EXPERIMENTAL

Conditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 400. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Allogeneic bone marrow transplant; Drug: Levetiracetam; Biological: Anti-thymocyte globulin; Radiation: Total body irradiation - 400

Interventions

Cyclophosphamide DRUG

Cyclophosphamide (Cy) 14.5 mg/kg/day intravenously (IV) on Days -6 and -5 and 50 mg/kg/day IV on Days +3 and +4.

Also known as: Cytoxan, Cy, CTX

Transplant - 200 cGy; Transplant - 400 cGy

Fludarabine DRUG

Fludarabine 30 mg/m\^2/day IV on Days -6, -5, -4, -3, and -2.

Also known as: Fludara

Transplant - 200 cGy; Transplant - 400 cGy

Mycophenolate mofetil DRUG

Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.

Also known as: MMF, CellCept

Transplant - 200 cGy; Transplant - 400 cGy

Sirolimus DRUG

The first dose of Sirolimus is 6 mg PO on Day +5. Further dosing is adjusted according to drug levels. Sirolimus is continued through Day +365.

Also known as: Rapamune

Transplant - 200 cGy; Transplant - 400 cGy

Allogeneic bone marrow transplant PROCEDURE

An allogeneic bone marrow transplant is a procedure that involves taking bone marrow from a donor and giving it to a recipient.

Also known as: Allo BMT

Transplant - 200 cGy; Transplant - 400 cGy

Total body irradiation - 200 RADIATION

200 centigray (cGy) in one fraction on Day -1.

Also known as: TBI

Transplant - 200 cGy

Levetiracetam DRUG

Given at 500 mg PO twice daily from Day -6 to Day +365.

Also known as: Keppra

Transplant - 200 cGy; Transplant - 400 cGy

Anti-thymocyte globulin BIOLOGICAL

Test dose of 0.5 mg/kg IV given on Day -9, then 2 mg/kg/day IV on Day -8 and -7.

Also known as: ATG, Thymoglobulin

Transplant - 200 cGy; Transplant - 400 cGy

Total body irradiation - 400 RADIATION

400 centigray (cGy) in one fraction on Day -1.

Also known as: TBI

Transplant - 400 cGy

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (2)

• Goldenberg M, Varadhan R, Gamper CJ, Cooke KR, Ambinder AJ, Symons HJ, Pecker LH, Jones RJ, Brodsky RA, Bolanos-Meade J. Bone marrow transplantation for sickle cell disease using post-transplantation cyclophosphamide and 400 cGy TBI. Blood Adv. 2026 Jan 22:bloodadvances.2025017413. doi: 10.1182/bloodadvances.2025017413. Online ahead of print.

  PMID: 41569644 DERIVED

• Bolanos-Meade J, Cooke KR, Gamper CJ, Ali SA, Ambinder RF, Borrello IM, Fuchs EJ, Gladstone DE, Gocke CB, Huff CA, Luznik L, Swinnen LJ, Symons HJ, Terezakis SA, Wagner-Johnston N, Jones RJ, Brodsky RA. Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial. Lancet Haematol. 2019 Apr;6(4):e183-e193. doi: 10.1016/S2352-3026(19)30031-6. Epub 2019 Mar 14.

  PMID: 30878319 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Mycophenolic Acid; Sirolimus; Levetiracetam; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Acetamides; Amides; Acetates; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: F Javier Bolanos Meade, MD
• Organization: Johns Hopkins University

fbolano2@jhmi.edu

4106146398

Study Officials

• Javier Bolanos-Meade, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 21, 2007
• Study Start: June 23, 2008
• Primary Completion: December 29, 2018
• Study Completion: December 29, 2018
• Last Updated: April 17, 2019
• Results First Posted: April 17, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)