Evaluating the Safety and Effectiveness of Bone Marrow Transplants in Children With Sickle Cell Disease (BMT CTN 0601)

NCT00745420 | Completed Phase 2 Results DMC

• 3 other identifiers: BMTCTN0601U01HL0692945U24CA076518
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 19

Brief Summary

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause organ damage, stroke, and intense pain episodes. A blood stem cell transplant is a treatment option for someone with a severe form of the disease. Prior to undergoing a transplant, people typically receive a conditioning regimen of high doses of chemotherapy and other medications to prepare the body to accept the transplant. A conditioning regimen that uses lower doses of chemotherapy and medications may be safer for transplant recipients. This study will evaluate the safety and effectiveness of blood stem cell transplants, using bone marrow from unrelated donors, in children with severe SCD who receive a reduced intensity conditioning regimen prior to the transplant.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Event-Free Survival (EFS)

  EFS is defined as percentage of participants that have not had an event. Primary or secondary graft rejection, disease recurrence, or death will count as events for this endpoint.

  2 years

Secondary Outcomes (13)

• Percentage of Participants With Overall Survival (OS)

  2 years

• Neutrophil and Platelet Recovery

  Up to 100 days

• Graft Rejection

  1 year

• Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD)

  100 days

• Percentage of Participants With Chronic GVHD

  1 year post-transplant

Study Arms (1)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

Bone Marrow Transplant with GVHD Prophylaxis Regimen

Biological: Hematopoietic Stem Cell Transplantation

Interventions

Hematopoietic Stem Cell Transplantation BIOLOGICAL

The stem cell transplant preparative regimen is listed below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant. * Alemtuzumab: Children weighing 10 kg or more will receive 10 mg, 15 mg, and 20 mg intravenously (IV) on Days -21, -20, and -19, respectively * Fludarabine: 30 mg/m\^2/day IV on Days -8 through -4 * Melphalan: 140 mg/m\^2 IV on Day -3 * Rest on Days -2 and -1 * Transplant occurs on Day 0 * GVHD prophylaxis: Tacrolimus or cyclosporine beginning Day -3, methotrexate (7.5 mg/m2/day) Day 1, 3 and 6 and methylprednisolone/prednisone on Day +7 to +28 followed by a taper if there is no GVHD

Also known as: Bone Marrow Transplant

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 3 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• SCD (genotype hemoglobin SS disease \[Hb SS\], genotype hemoglobin SC disease \[HbSC\],sickle ß°\[Sß°\] thalassemia, or sickle ß\^+\[Sß\^+\]thalassemia) with one or more of the following:
• Patients must have symptomatic SCD (genotype Hb SS, Hb SC, Sß° thalassemia or Sß+ thalassemia), AND have 1 or more of the following clinical complications:(i) Clinically significant neurologic event (stroke) or any neurologic deficit lasting more than 24 hours that is accompanied by an infarct on cerebral MRI; OR (ii) patients who have a Transcranial Doppler (TCD) velocity that exceeds 200 cm/sec by the non-imaging technique (or TCD measurement greater than 185 cm/sec by the imaging technique) measured at a minimum of 2 separate occasions one month or more apart; OR,
• Minimum of two episodes of acute chest syndrome in the 2 years before study entry, defined as new pulmonary alveolar consolidation involving at least one complete lung segment (associated with acute symptoms including fever, chest pain, tachypnea, wheezing, rales, or cough that is not attributed to asthma or bronchiolitis) despite adequate supportive care measures
• History of 3 or more severe pain events per year in the 2 years before study entry
• Lansky/Karnofsky performance score greater than or equal to 40
• Patients must have an unrelated adult bone marrow donor who is Human Leukocyte Antigen (HLA)-matched at 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
• Patients with adequate physical function: a)Cardiac: Left ventricular ejection fraction (LVEF) greater than 40%, or LV shortening fraction greater than 26%; b) Pulmonary: Pulse oxymetry with a baseline O2 saturation of greater than or equal to 85% is required for all patients, Carbon Monoxide Diffusing Capacity (DLCO) greater than 40% (corrected for hemoglobin) for patients in whom pulmonary function testing can be performed; c) Renal: Serum creatinine less than or equal to 1.5 x upper limit of normal for age and glomerular filtration rate (GFR) greater than 100 mL/min/1.73 m. For patients older than or equal to 16 years of age, GFR should be greater than 70 mL/min/1.73 m\^2; d) Hepatic: Serum conjugated (direct) bilirubin less than 2x upper limit of normal for age as per local laboratory; alanine transaminase (ALT) and aspartate transaminase (AST) less than 5 times upper limit of normal as per local laboratory.
• If the patient has been receiving chronic transfusion therapy for more than or equal to 1 year AND has clinical evidence of iron overload (serum ferritin level of greater than 1000 ng/ml), a liver biopsy shall be obtained within 90 days of starting conditioning therapy (alemtuzumab). Histologic exam of the liver must document absence of bridging fibrosis or cirrhosis of the liver. In other cases, a liver biopsy is optional.
• Hemoglobin S (Hb S) level less than or equal to 45%, seven days prior to initiation of alemtuzumab

You may not qualify if:

• Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen
• Pregnant or breastfeeding
• Patients with 8/8 HLA-matched family donors able to donate
• Seropositivity for HIV
• Prior allogeneic marrow or stem cell transplant
• Iron chelation must be discontinued more than or equal to 48 hours before initiating the conditioning regimen
• Hydroxyurea (if receiving this therapy) must be discontinued more than or equal to 48 hours before initiating the conditioning regimen

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Cancer Institute (NCI): collaborator
• National Marrow Donor Program: collaborator
• Sickle Cell Disease Clinical Research Network: collaborator

Study Sites (19)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

Children's Hospital of New Orleans/LSUMC CCOP

New Orleans, Louisiana, 70118, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48105, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospital and Clinics

Kansas City, Missouri, 64108, United States

Location

Washington University, St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Cohen Children's Hospital

New Hyde Park, New York, 11040, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (5)

• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

  PMID: 16338616 BACKGROUND

• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.

  PMID: 7581076 BACKGROUND

• Shenoy S, Eapen M, Panepinto JA, Logan BR, Wu J, Abraham A, Brochstein J, Chaudhury S, Godder K, Haight AE, Kasow KA, Leung K, Andreansky M, Bhatia M, Dalal J, Haines H, Jaroscak J, Lazarus HM, Levine JE, Krishnamurti L, Margolis D, Megason GC, Yu LC, Pulsipher MA, Gersten I, DiFronzo N, Horowitz MM, Walters MC, Kamani N. A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016 Nov 24;128(21):2561-2567. doi: 10.1182/blood-2016-05-715870. Epub 2016 Sep 13.

  PMID: 27625358 RESULT

• Martens MJ, Logan BR. Statistical rules for safety monitoring in clinical trials. Clin Trials. 2024 Apr;21(2):152-161. doi: 10.1177/17407745231203391. Epub 2023 Oct 25.

  PMID: 37877375 DERIVED

• Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.

  PMID: 36240296 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hematopoietic Stem Cell Transplantation; Bone Marrow Transplantation

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)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Tissue Transplantation

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: August 29, 2008
• First Posted: September 3, 2008
• Study Start: August 1, 2008
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2016
• Last Updated: December 9, 2022
• Results First Posted: December 26, 2017

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public

Locations

US (19)