Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia

NCT00034528 | Terminated Phase 2

• 2 other identifiers: DAIT DF/HCC 01-098P01 A 129530
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.

Conditions

Hemoglobinopathies; Anemia, Sickle Cell; Hemoglobin SC Disease; Thalassemia; Thalassemia Major

Outcome Measures

Primary Outcomes (1)

• Evidence of engraftment of donor hematopoietic cells following administration of low doses of busulfan and fludarabine

  Throughout study

Secondary Outcomes (3)

• Solid organ toxicity related to the conditioning regimen

  Throughout study

• Incidence of grade II, III, or IV acute graft versus host disease (GVHD)

  Throughout study

• Level of disease response

  Throughout study

Study Arms (1)

Allogeneic stem cell transplantation

EXPERIMENTAL

Participants will receive a nonmyeloablative conditioning regimen of fludarabine and busulfan prior to allogeneic peripheral blood stem cell (CD34+) infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis.

Drug: Busulfan; Drug: Fludarabine; Drug: FK506; Drug: Prednisone

Interventions

Busulfan DRUG

0.8 mg/kg/d administered as a single intravenous infusion over 3 hours for 4 days. All infusions are anticipated to be given in the outpatient clinic.

Also known as: Busulfex

Allogeneic stem cell transplantation

Fludarabine DRUG

30 mg/m\^2/d administered as a bolus infusion over 30 minutes for 4 days. All infusions are anticipated to be given in the outpatient clinic.

Also known as: Fludara, Oforta

Allogeneic stem cell transplantation

FK506 DRUG

0.15 mg/kg taken orally daily for 12 to 14 weeks

Also known as: Prograf, Tacromilus

Allogeneic stem cell transplantation

Prednisone DRUG

0.5 mg/kg taken orally four times daily on Day 7 and increase to 1 mg/kg taken orally four times daily on Day 14. Participants will continue regimen until Day 30 before a 20-25% taper per week.

Allogeneic stem cell transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must:
• Have related donors who are identical at 6 human leukocyte antigens (HLA) loci (A, B and DR) by molecular typing
• Have a performance status from 0-2
• Give written informed consent
• Patients with sickle cell disease should have 1 or more of the following:
• Acute chest syndrome requiring recurrent hospitalization or exchange transfusion
• Nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours
• Recurrent vaso-occlusive pain (2 episodes or more per year) or recurrent priapism
• Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate 30-50 percent of normal predicted value)
• Bilateral proliferative retinopathy and major visual impairment in at least 1 eye
• Osteonecrosis of multiple joints
• Patients with thalassemia should have 1 or more of the following:
• Transfusion dependence, defined as a transfusion requirement of greater than or equal to 6 units of packed red blood cells over the past 12 months
• Iron overload, defined as serum ferritin greater than 500 mcg/L in the absence of infection or biopsy-proven iron overload
• Presence of 2 or more alloantibodies against red cell antigens

You may not qualify if:

• Pregnancy
• Acute hepatitis (transaminases greater than 3 times the normal value)
• Cardiac ejection fraction less than 30 percent
• Severe renal impairment (glomerular filtration rate less than 30 percent of predicted normal value)
• Severe residual functional neurologic impairment (other than hemiplegia alone)
• Seropositivity for the human immunodeficiency virus (HIV)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Dana-Farber Cancer Institute/Harvard Cancer Center, Brigham and Women's Hospital and Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (7)

• Walters MC, Storb R, Patience M, Leisenring W, Taylor T, Sanders JE, Buchanan GE, Rogers ZR, Dinndorf P, Davies SC, Roberts IA, Dickerhoff R, Yeager AM, Hsu L, Kurtzberg J, Ohene-Frempong K, Bunin N, Bernaudin F, Wong WY, Scott JP, Margolis D, Vichinsky E, Wall DA, Wayne AS, Pegelow C, Redding-Lallinger R, Wiley J, Klemperer M, Mentzer WC, Smith FO, Sullivan KM. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood. 2000 Mar 15;95(6):1918-24.

  PMID: 10706855 BACKGROUND

• Gomez-Almaguer D, Ruiz-Arguelles GJ, Ruiz-Arguelles A, Gonzalez-Llano O, Cantu OE, Hernandez NE. Hematopoietic stem cell allografts using a non-myeloablative conditioning regimen can be safely performed on an outpatient basis: report of four cases. Bone Marrow Transplant. 2000 Jan;25(2):131-3. doi: 10.1038/sj.bmt.1702100.

  PMID: 10673669 BACKGROUND

• Krishnamurti L, Blazar BR, Wagner JE. Bone marrow transplantation without myeloablation for sickle cell disease. N Engl J Med. 2001 Jan 4;344(1):68. doi: 10.1056/NEJM200101043440119. No abstract available.

  PMID: 11187121 BACKGROUND

• Andersson BS, Madden T, Tran HT, Hu WW, Blume KG, Chow DS, Champlin RE, Vaughan WP. Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study. Biol Blood Marrow Transplant. 2000;6(5A):548-54. doi: 10.1016/s1083-8791(00)70064-4.

  PMID: 11071260 BACKGROUND

• Wu CJ, Krishnamurti L, Kutok JL, Biernacki M, Rogers S, Zhang W, Antin JH, Ritz J. Evidence for ineffective erythropoiesis in severe sickle cell disease. Blood. 2005 Nov 15;106(10):3639-45. doi: 10.1182/blood-2005-04-1376. Epub 2005 Aug 9.

  PMID: 16091448 BACKGROUND

• Wu CJ, Gladwin M, Tisdale J, Hsieh M, Law T, Biernacki M, Rogers S, Wang X, Walters M, Zahrieh D, Antin JH, Ritz J, Krishnamurti L. Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis. Br J Haematol. 2007 Nov;139(3):504-7. doi: 10.1111/j.1365-2141.2007.06803.x. No abstract available.

  PMID: 17910640 BACKGROUND

• Wu CJ, Hochberg EP, Rogers SA, Kutok JL, Biernacki M, Nascimento AF, Marks P, Bridges K, Ritz J. Molecular assessment of erythroid lineage chimerism following nonmyeloablative allogeneic stem cell transplantation. Exp Hematol. 2003 Oct;31(10):924-33. doi: 10.1016/s0301-472x(03)00227-3.

  PMID: 14550808 RESULT

MeSH Terms

Conditions

Hemoglobinopathies; Anemia, Sickle Cell; Hemoglobin SC Disease; Thalassemia; beta-Thalassemia

Interventions

Busulfan; fludarabine; fludarabine phosphate; Tacrolimus; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Catherine J. Wu, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 30, 2002
• First Posted: May 1, 2002
• Study Start: September 1, 2001
• Primary Completion: November 1, 2003
• Study Completion: November 1, 2003
• Last Updated: May 1, 2013

Record last verified: 2013-04

Locations

US (1)