HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity

NCT02435901 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 08057
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickle Cell Disease; Beta Thalassemia-Major

Keywords

Reduced Intensity Conditioning Regimen

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sustained Cell Engraftment of Donor Cells

  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 Outcomes (2)

• Assessment of Treatment Related Mortality and Morbidity

  2 years

• Event Free Survival; Number of Participants Who Survived at 2 Years

  2 years

Study Arms (1)

Reduced Intensity Regimen

EXPERIMENTAL

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); Drug: Fludarabine; Drug: Melphalan; Drug: Cyclosporine; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Biological: Hematopoietic Stem Cell Transplantation

Interventions

alemtuzumab (Campath IH) DRUG

Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17

Also known as: Campath-IH

Reduced Intensity Regimen

Fludarabine DRUG

Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4.

Reduced Intensity Regimen

Melphalan DRUG

Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2.

Reduced Intensity Regimen

Cyclosporine DRUG

Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to stem cell infusion

Reduced Intensity Regimen

Mycophenolate mofetil DRUG

Immunosuppressant to prevent graft vs host disease is given on Day -1.

Reduced Intensity Regimen

Tacrolimus DRUG

Immunosuppressant to prevent graft vs host disease is given Day -1 prior to stem cell infusion

Reduced Intensity Regimen

Hematopoietic Stem Cell Transplantation BIOLOGICAL

Human Leukocyte Antigen (HLA) matched or mismatched; related or unrelated hematopoietic stem cells to be transplanted on Day 0.

Reduced Intensity Regimen

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Hepatomegaly.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

Location

Related Publications (1)

• King AA, Kamani N, Bunin N, Sahdev I, Brochstein J, Hayashi RJ, Grimley M, Abraham A, Dioguardi J, Chan KW, Douglas D, Adams R, Andreansky M, Anderson E, Gilman A, Chaudhury S, Yu L, Dalal J, Hale G, Cuvelier G, Jain A, Krajewski J, Gillio A, Kasow KA, Delgado D, Hanson E, Murray L, Shenoy S. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015 Dec;90(12):1093-8. doi: 10.1002/ajh.24183. Epub 2015 Oct 6.

  PMID: 26348869 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia

Interventions

Alemtuzumab; fludarabine; Melphalan; Cyclosporine; Mycophenolic Acid; Tacrolimus; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Indira Sahdev, MD
• Organization: Northwell Health System Cohen Children's Medical Center of NY

isahdev@northwell.edu

7184703460

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2015
• First Posted: May 6, 2015
• Study Start: December 1, 2008
• Primary Completion: March 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 24, 2021
• Results First Posted: November 5, 2020

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)