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Stem Cell Transplant in Sickle Cell Disease and Thalassemia

Primary Purpose

Sickle Cell Disease, Beta Thalassemia

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Busulfan

Fludarabine

Alemtuzumab

Allogeneic stem cell transplant

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring stem cell transplant, sickle cell disease, thalassemia, moderately ablative, cord blood transplant, matched family donor

Eligibility Criteria

1 Month - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

SCD group

BT group

Arm Description

Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Outcomes

Primary Outcome Measures

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)

To examine if giving lower doses of chemotherapy will result in less severe side-effects but with permanent control of the disease.

Secondary Outcome Measures

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

To examine if giving lower doses of chemotherapy and bone marrow replacement can result in control of the disease.

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

To examine if giving lower doses of chemotherapy will result in successful bone marrow replacement.

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

To examine if giving lower doses of chemotherapy with bone marrow replacement will result in good control of the disease.

Quality of life (QOL) score

To determine the impact of moderately ablative stem cell transplant on quality of life and neurocognitive functioning with SCD over time

Incidence of primary and secondary graft failure

To collect data on graft failure

Percent of mixed donor chimerism

To collect data on donor chimerism

Full Information

NCT ID

NCT00408447

First Posted

December 6, 2006

Last Updated

March 20, 2023

Sponsor

Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT00408447

Brief Title

Stem Cell Transplant in Sickle Cell Disease and Thalassemia

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 2004 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease, Beta Thalassemia

Keywords

stem cell transplant, sickle cell disease, thalassemia, moderately ablative, cord blood transplant, matched family donor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SCD group

Arm Type

Other

Arm Description

Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Arm Title

BT group

Arm Type

Other

Arm Description

Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Intervention Type

Drug

Intervention Name(s)

Busulfan

Other Intervention Name(s)

Busulfex

Intervention Description

Busulfan 4 mg/kg/d x 4d

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludara

Intervention Description

Fludarabine 30 mg/m2/d x 6d

Intervention Type

Drug

Intervention Name(s)

Alemtuzumab

Other Intervention Name(s)

Campath

Intervention Description

Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d

Intervention Type

Procedure

Intervention Name(s)

Allogeneic stem cell transplant

Other Intervention Name(s)

Related Bone Marrow, Related Cord Blood

Intervention Description

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.

Primary Outcome Measure Information:

Title

Description

To examine if giving lower doses of chemotherapy will result in less severe side-effects but with permanent control of the disease.

Time Frame

Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years

Secondary Outcome Measure Information:

Title

Description

To examine if giving lower doses of chemotherapy and bone marrow replacement can result in control of the disease.

Time Frame

days 60, 100, 180, 365, 730

Title

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

Description

To examine if giving lower doses of chemotherapy will result in successful bone marrow replacement.

Time Frame

as clinically appropriate

Title

Description

To examine if giving lower doses of chemotherapy with bone marrow replacement will result in good control of the disease.

Time Frame

6mos, 1 yr, 2 yr

Title

Quality of life (QOL) score

Description

To determine the impact of moderately ablative stem cell transplant on quality of life and neurocognitive functioning with SCD over time

Time Frame

Day +180; year 1, 3, 5, 10

Title

Incidence of primary and secondary graft failure

Description

To collect data on graft failure

Time Frame

Day +42, +60,

Title

Percent of mixed donor chimerism

Description

To collect data on donor chimerism

Time Frame

Day +30, 60, 100, 180, 365, 730, and 1005

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Month

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Monica Bhatia, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

15931629

Citation

Satwani P, Harrison L, Morris E, Del Toro G, Cairo MS. Reduced-intensity allogeneic stem cell transplantation in adults and children with malignant and nonmalignant diseases: end of the beginning and future challenges. Biol Blood Marrow Transplant. 2005 Jun;11(6):403-22. doi: 10.1016/j.bbmt.2005.04.002.

Results Reference

background

PubMed Identifier

14730337

Citation

Del Toro G, Satwani P, Harrison L, Cheung YK, Brigid Bradley M, George D, Yamashiro DJ, Garvin J, Skerrett D, Bessmertny O, Wolownik K, Wischhover C, van de Ven C, Cairo MS. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant. 2004 Mar;33(6):613-22. doi: 10.1038/sj.bmt.1704399.

Results Reference

background

PubMed Identifier

24797180

Citation

Bhatia M, Jin Z, Baker C, Geyer MB, Radhakrishnan K, Morris E, Satwani P, George D, Garvin J, Del Toro G, Zuckerman W, Lee MT, Licursi M, Hawks R, Smilow E, Baxter-Lowe LA, Schwartz J, Cairo MS. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease. Bone Marrow Transplant. 2014 Jul;49(7):913-20. doi: 10.1038/bmt.2014.84. Epub 2014 May 5.

Results Reference

derived

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Stem Cell Transplant in Sickle Cell Disease and Thalassemia

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