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Stem Cell Transplantation for Sickle Cell Anemia

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ClinicalTrials.gov Identifier: NCT01877837
Recruitment Status : Active, not recruiting
First Posted : June 14, 2013
Last Update Posted : February 12, 2018
Information provided by (Responsible Party):
Hackensack University Medical Center

Brief Summary:
This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to vaso-occlusion, which causes irreversible damage in almost all systems in the body, including the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Alemtuzumab Drug: Fludarabine Drug: Melphalan Procedure: Stem Cells Phase 3

Detailed Description:

Primary objective:

1) To determine disease free survival (DFS) at one year after matched sibling transplant using either bone marrow (BM), peripheral blood stem cells (PBSC), or umbilical cord blood (UCB) after a conditioning regimen consisting of Alemtuzumab, Fludarabine, and Melphalan in patients 2-30 y/o

Secondary objectives:

  1. Overall survival
  2. Rate of neutrophil and platelet engraftment for BM vs. UCB
  3. Incidence of graft failure
  4. Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)
  5. Incidence of chronic GVHD
  6. Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)
  7. Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus
  8. Incidence of invasive fungal disease
  9. Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Intensity Stem Cell Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
Study Start Date : June 2011
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Related donor

Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.

1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.

Day Treatment

  • -22 Alemtuzumab 3mg IV (test dose)
  • -21 Alemtuzumab 10mg IV
  • -20 Alemtuzumab 15mg IV
  • -19 Alemtuzumab 20mg IV
  • -8 Fludarabine 30mg/m2 IV
  • -7 Fludarabine 30mg/m2 IV
  • -6 Fludarabine 30mg/m2 IV
  • -5 Fludarabine 30mg/m2 IV
  • -4 Fludarabine 30mg/m2 IV
  • -3 Melphalan 140mg/m2 IV
  • -2 Rest Day
  • -1 Rest Day
  • 0 Stem Cell Infusion
Drug: Alemtuzumab

Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)]

b) Medications

i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below

Other Name: Alemtuzumab (Campath)
Drug: Fludarabine
I. Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine
Other Name: Fludarabine (Fludara)
Drug: Melphalan

I. Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. *Entire dose must be infused within 60 minutes of reconstitution in Pharmacy.

II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion.

Other Name: Melphalan (Alkeran)
Procedure: Stem Cells
Infusion of Hematopoietic Stem Cells

Primary Outcome Measures :
  1. Graft Failure [ Time Frame: 1 year ]

    Primary endpoint:

    In each group, the DFS at the 1 year endpoint will be estimated using the Kaplan Meier product limit estimator. The frequencies of the events, ie graft failure, will be enumerated and presented.

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]

    Secondary endpoints:

    Overall survival: The distribution of time to death from any cause will be estimated by Kaplan- Meier product limit function and plotted. The overall survival will be measured from the time of transplant to any death and patients will be followed for 2 years.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient Eligibility

    1) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight)

    1. Age 2-30
    2. Hb SS, S-thal0, S-thal+, SC
    3. Evidence of ongoing hemolysis: Hb<10, retic >5%, LDH > 500, TB>2
    4. Karnofsky/Lansky score >50
    5. LVSF>26% or LVEF>40%
    6. DLCO >40% or O2 sat >85% for those patients that can't perform PFTs
    7. GFR >70 and serum creatinine < 1.5 * ULN for age
    8. ALT and AST < 5 x ULN, direct bilirubin <2 x ULN
    9. If the patient has been on chronic transfusion or has a ferritin >1000, liver biopsy should be done and show no evidence of bridging fibrosis or cirrhosis
  • Exclusion criteria

    1. Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen
    2. Pregnant or breastfeeding
    3. HIV positive
    4. Written informed consent not obtained

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01877837

United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
Hackensack University Medical Center
Principal Investigator: Jennifer Krajewski, MD Hackensack University Medical Center

Responsible Party: Hackensack University Medical Center
ClinicalTrials.gov Identifier: NCT01877837     History of Changes
Other Study ID Numbers: Pro00001894
First Posted: June 14, 2013    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018

Keywords provided by Hackensack University Medical Center:
Stem cell transplant
Sickle cell
Stem cell transplantation

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists