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Stem Cell Transplantation for Sickle Cell Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01877837
Recruitment Status : Active, not recruiting
First Posted : June 14, 2013
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
Hackensack Meridian Health

Tracking Information
First Submitted Date  ICMJE June 12, 2013
First Posted Date  ICMJE June 14, 2013
Last Update Posted Date April 27, 2020
Study Start Date  ICMJE June 2011
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 13, 2013)
Graft Failure [ Time Frame: 1 year ]
Primary endpoint: In each group, the EFS 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2013)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stem Cell Transplantation for Sickle Cell Anemia
Official Title  ICMJE Reduced Intensity Stem Cell Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Interventions:
  • Drug: Alemtuzumab
  • Drug: Fludarabine
  • Drug: Melphalan
  • Procedure: Stem Cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 9, 2018)
26
Original Estimated Enrollment  ICMJE
 (submitted: June 13, 2013)
40
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01877837
Other Study ID Numbers  ICMJE Pro00001894
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hackensack Meridian Health
Study Sponsor  ICMJE Hackensack Meridian Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jennifer Krajewski, MD Hackensack Meridian Health
PRS Account Hackensack Meridian Health
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP