Stem Cell Transplant in Sickle Cell Disease and Thalassemia

March 20, 2023 updated by: Columbia University

Allogeneic Stem Cell Transplant to Induce Mixed Donor Chimerism in Patients With Sickle Cell Disease and Thalassemia

The primary purpose of this study is to see if giving lower doses of chemotherapy (moderately ablative) will result in successful bone marrow replacement without as severe side-effects but with permanent control of the disease. Patients will receive a chemotherapy regimen with busulfan, fludarabine, and alemtuzumab followed by an infusion of stem cells, either from a family-related or cord-blood matched donor.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Sickle cell disease is a genetic disorder in which a mutation in the beta chain of human hemoglobin results in abnormal blood hemoglobin, causing red blood cells to sickle under stress with resulting symptoms including severe pains and strokes. Beta thalassemia is another genetic disorder in which there are abnormal beta hemoglobin chains, causing anemia. In both disorders, frequent red blood cell transfusions may be required to sustain life, but these often result in complications including multiple hospitalizations, iron overload, or bacterial or viral infections such as hepatitis. Standard drugs and therapies used in the treatment of sickle cell disease and/or beta thalassemia provide only supportive care, and may result in long-term side effects, and inadequate control of the disease process. Bone marrow transplant has been increasingly used for the long-term treatment and cure of sickle cell disease and beta thalassemia. Although, not without acute and potential long term side effects, this alternative offers long term control and potential cure of the disease. Most of the side effects seen with bone marrow transplant are directly related to the high intensity of chemotherapy used (ablative).

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Sickle Cell Disease:

  • Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin Sickle Cell (SC) or S 0/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia with hemoglobin (HgB) ≤10 mg/dL
  • Age ≤30
  • Matched sibling donor and asymptomatic, or 8/8 human leukocyte antigen (HLA) matched unrelated adult donor

Patient must have adequate organ function as below:

  • Adequate renal function defined as serum creatinine ≤1.5 x normal, or Creatinine clearance or radioisotope glomerular filtration rate (GFR) >100 ml/min/1.73 m2 or >70ml/min/1.73m2 for patients >16 years old
  • Adequate liver function defined as serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) < 5.0 x normal
  • Adequate Cardiac Function defined as shortening fraction of ≥28% by echocardiogram, or ejection fraction of ≥48% by radionuclide angiogram or echocardiogram
  • Adequate pulmonary function defined as corrected Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% by pulmonary function test, or for children who are unable to perform DLCO maneuver ≥85% O2 saturation, no evidence of dyspnea at rest

Exclusion criteria:

General

  • Karnofsky/Lansky Performance Score <60%
  • Demonstrated lack of compliance with medical care
  • Pregnant or nursing
  • 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.

Histologic Exam of Liver (liver biopsy) with bridging fibrosis or cirrhosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: SCD group
Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
Drug: Busulfan
Busulfan 4 mg/kg/d x 4d
Other Names:
  • Busulfex
Drug: Fludarabine
Fludarabine 30 mg/m2/d x 6d
Other Names:
  • Fludara
Drug: Alemtuzumab
Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d
Other Names:
  • Campath
Procedure: Allogeneic stem cell transplant
Allogeneic stem cells will be given on day 0 (after chemotherapy conditioning)obtained either from a family donor (first degree relative) or sibling cord blood donor.
Other Names:
  • Related Bone Marrow
  • Related Cord Blood
Other: BT group
Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
Drug: Busulfan
Busulfan 4 mg/kg/d x 4d
Other Names:
  • Busulfex
Drug: Fludarabine
Fludarabine 30 mg/m2/d x 6d
Other Names:
  • Fludara
Drug: Alemtuzumab
Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d
Other Names:
  • Campath
Procedure: Allogeneic stem cell transplant
Allogeneic stem cells will be given on day 0 (after chemotherapy conditioning)obtained either from a family donor (first degree relative) or sibling cord blood donor.
Other Names:
  • Related Bone Marrow
  • Related Cord Blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of toxicity associated with moderately ablative therapy (busulfan/fludarabine/alemtuzumab) and allogeneic stem cell transplantation in selected patients with Sickle Cell Disease (SCD) and Beta Thalassemia (BT)
Time Frame: Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years
To examine if giving lower doses of chemotherapy will result in less severe side-effects but with permanent control of the disease.
Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to donor hematological reconstitution (neutrophil, red blood cell and platelet recovery) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT
Time Frame: days 60, 100, 180, 365, 730
To examine if giving lower doses of chemotherapy and bone marrow replacement can result in control of the disease.
days 60, 100, 180, 365, 730
Incidence of acute and chronic graft versus host disease (GVHD) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT
Time Frame: as clinically appropriate
To examine if giving lower doses of chemotherapy will result in successful bone marrow replacement.
as clinically appropriate
Percent of patients who have either a complete, very good partial, partial or no response (clinical/laboratory) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT
Time Frame: 6mos, 1 yr, 2 yr
To examine if giving lower doses of chemotherapy with bone marrow replacement will result in good control of the disease.
6mos, 1 yr, 2 yr
Quality of life (QOL) score
Time Frame: Day +180; year 1, 3, 5, 10
To determine the impact of moderately ablative stem cell transplant on quality of life and neurocognitive functioning with SCD over time
Day +180; year 1, 3, 5, 10
Incidence of primary and secondary graft failure
Time Frame: Day +42, +60,
To collect data on graft failure
Day +42, +60,
Percent of mixed donor chimerism
Time Frame: Day +30, 60, 100, 180, 365, 730, and 1005
To collect data on donor chimerism
Day +30, 60, 100, 180, 365, 730, and 1005

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2004

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

December 6, 2006

First Submitted That Met QC Criteria

December 6, 2006

First Posted (Estimate)

December 7, 2006

Study Record Updates

Last Update Posted (Actual)

March 22, 2023

Last Update Submitted That Met QC Criteria

March 20, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAA7701
  • CHNY-01-503 (Other Identifier: CU)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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