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Stem Cell Transplantation for Sickle Cell Anemia

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ClinicalTrials.gov Identifier: NCT01877837
Recruitment Status : Completed
First Posted : June 14, 2013
Results First Posted : November 7, 2022
Last Update Posted : November 7, 2022
Sponsor:
Information provided by (Responsible Party):
Hackensack Meridian Health

Study Description
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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 two years after matched sibling transplant using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab, Fludarabine, and Melphalan for patients 2-30 y/o

Secondary objectives:

  1. Overall survival
  2. Rate of neutrophil and platelet engraftment for BM
  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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Intensity Matched Sibling Bone Marrow Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
Study Start Date : June 2011
Actual Primary Completion Date : September 2021
Actual Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Graft Failure [ Time Frame: 2 years ]

    Primary endpoint:

    In each group, the Number of participants with Graft Failure at the 2 years endpoint will be estimated using the Kaplan Meier product limit estimator.



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.



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

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
Contacts and Locations
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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


Locations
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United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
Hackensack Meridian Health
Investigators
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Principal Investigator: Jennifer Krajewski, MD Hackensack Meridian Health
  Study Documents (Full-Text)

Documents provided by Hackensack Meridian Health:
Study Protocol and Statistical Analysis Plan  [PDF] April 11, 2019

More Information
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Responsible Party: Hackensack Meridian Health
ClinicalTrials.gov Identifier: NCT01877837    
Other Study ID Numbers: Pro00001894
First Posted: June 14, 2013    Key Record Dates
Results First Posted: November 7, 2022
Last Update Posted: November 7, 2022
Last Verified: October 2022
Keywords provided by Hackensack Meridian Health:
Stem cell transplant
Sickle cell
Stem cell transplantation
Related
Unrelated
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Fludarabine
Fludarabine phosphate
Melphalan
Alemtuzumab
 Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological