HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity

July 30, 2021 updated by: Northwell Health

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN PATIENTS WITH HIGH RISK HEMOGLOBINOPATHIES LIKE SICKLE CELL DISEASE AND β-THALESSEMIA-MAJOR USING REDUCED INTENSITY CONDITIONING REGIMEN

This study will evaluate the use of reduced intensity conditioning regimen in patients with high risk hemoglobinopathy Sickle Cell and B-Thalassemia Major in combination with standard immunosuppressive medications, followed by a routine stem cell transplant in order to assess whether or not it is as effective as myeloablative high dose chemotherapy and transplant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Standard myeloablative regimens are toxic to non-hematopoietic tissue and are associated with treatment related mortality and morbidity (TRM). Preparative regimens that are not myeloablative are associated with a greatly decreased incidence of TRM. In addition to providing a less toxic regimen, the reduced intensity chemotherapy preparative regimen also remains immunosuppressive enough to allow donor engraftment. Recent report of non-myeloablative regimens which resulted in engraftment of allogeneic stem cell in hematological malignancies raises the possibility that this conditioning regimen might be useful in achieving engraftment in non hematological disorder.

In an effort to achieve stable engraftment with any suitable donor stem cell source and to minimize toxicity the investigators have developed a new reduced intensity conditioning regimen for high risk hemoglobinopathies with the main aim of significantly suppressing the recipient's immune system and facilitate engraftment.

Non-myeloablative or reduced-intensity immunosuppressive preparative regimens have achieved a stable, mixed chimerism engraftment and successful allogeneic bone marrow transplants.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2
  • Phase 1

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 Hyde Park, New York, United States, 11040
        • Cohen Children's Medical Center of New York

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 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient Inclusion Criteria for Sickle Cell Disease
  • Patients at least one year of age to less than or equal to 21 years of age with (Sickle Cell Disease-SS or Sickle Cell-S-β-Thalassemia and with one or more of the following disease complications:
  • Development of stroke on chronic transfusion protocol.
  • Allosensitization on chronic transfusion therapy
  • Impaired neuropsychological function and abnormal MRI scan
  • Abnormal Transcranial Doppler studies
  • Acute chest syndrome (2 to 3 episodes of acute chest syndrome in last 3 to 4 years).
  • Ferritin level < 1500 mg/ml
  • Recurrent painful priapism; 3-4 episodes/year requiring intervention.
  • Recurrent vaso-occlusive crisis of at least 3 to 4 episodes/year.
  • Osteonecrosis of multiple bones with documented destructive changes.
  • Signed informed consent
  • Patients physically and psychologically capable of undergoing transplantation and a period of strict isolation.
  • Ferritin < 1500
  • Liver Iron Concentration < 6mg/g

Patient Inclusion Criteria for β Thalassemia major Patients less than or equal to 21 years of age with B- Thalassemia major on routine monthly transfusion protocol or with one or more of the following complications;

  1. Hepatomegaly.
  2. Liver biopsy revealing evidence of portal fibrosis as A) Mild B) Moderate
  3. Ferritin level≤ 1500ng/ml
  4. Liver Iron Concentration (LIC) < 6mg/g

Exclusion Criteria:

  • Exclusion Criteria for Both Sickle Cell and β Thalassemia Major Patient
  • HIV positive result confirmed by Western Blot.
  • Pregnancy (Pregnancy testing for females of child-bearing age will be performed and those with a positive serum β-Human Chorionic Gonadotropin will be excluded) and lactating females.
  • Creatinine greater than two times the upper limit of normal for the laboratory,
  • Pulmonary disease with FVC, FEV1 or DLCO parameters < 50% predicted (corrected for hemoglobin) or stage 3 or 4 sickle lung disease.
  • Cardiac insufficiency or coronary artery disease requiring treatment
  • Active infection requiring systemic antibiotic therapy with antibacterial, antifungal or antiviral agents
  • Lansky performance score <70%- (Appendix B)
  • Acute hepatitis/biopsy evidence of cirrhosis.
  • Pulmonary Hypertension

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reduced Intensity Regimen
Administration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients <10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients > 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused.
Drug: alemtuzumab (Campath IH)
Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17
Other Names:
  • Campath-IH
Drug: Fludarabine
Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4.
Drug: Melphalan
Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2.
Drug: Cyclosporine
Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to stem cell infusion
Drug: Mycophenolate mofetil
Immunosuppressant to prevent graft vs host disease is given on Day -1.
Drug: Tacrolimus
Immunosuppressant to prevent graft vs host disease is given Day -1 prior to stem cell infusion
Biological: Hematopoietic Stem Cell Transplantation
Human Leukocyte Antigen (HLA) matched or mismatched; related or unrelated hematopoietic stem cells to be transplanted on Day 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Sustained Cell Engraftment of Donor Cells
Time Frame: 1 year
Sustained stem cell engraftment of donor cells will be evaluated by chimerism (FISH fluorescence in situ hybridization OR VNTR (Variable Number of Tandem Repeats), based on recipient/donor gender, at 30 days, 100 days, 6 months and 1 year following the use of reduced intensity conditioning.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Treatment Related Mortality and Morbidity
Time Frame: 2 years
Patients will be evaluated for incidence and severity of graft versus host disease, infection, and cardiopulmonary complications.
2 years
Event Free Survival; Number of Participants Who Survived at 2 Years
Time Frame: 2 years
29 participants will be evaluated for Event Free Survival.
2 years

Collaborators and Investigators

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

Sponsor

Northwell Health

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

December 1, 2008

Primary Completion (Actual)

March 1, 2019

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

April 24, 2015

First Submitted That Met QC Criteria

May 5, 2015

First Posted (Estimate)

May 6, 2015

Study Record Updates

Last Update Posted (Actual)

August 24, 2021

Last Update Submitted That Met QC Criteria

July 30, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08057

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Outcome data to include study findings.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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