A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease

NCT01279616 | Terminated Phase 2 Results DMC

• 1 other identifier: 09-00383
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Majority of patients who are eligible for allogeneic HSCT for cure of severe sickle cell disease lack a matched family donor. This study aims for cure of sickle cell disease by performing unrelated donor (outside family) allogeneic HSCT. Donors or unrelated cord blood units will be selected from the NMDP database. It is designed to estimate the safety of a novel reduced toxicity, yet an immunosuppressive and myeloablative preparative regimen. This is meant for patients \<21 years old who have severe complications from sickle cell and do not have matched sibling donors in the family to undergo stem cell transplant. Patients will undergo transplant using unrelated donor stem cells after receiving the protocol therapy. They will be followed for 1 year to monitor for engraftment of donor cells and complications like graft versus host disease (GVHD), infections and death.

Conditions

Sickle Cell Disease

Keywords

sickle cell; stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Event-free Survival

  Event-free survival

  1 year

Study Arms (1)

Hematopoietic Stem Cell Transplant

EXPERIMENTAL

Stem cell infusion on Day 0.

Drug: Fludarabine monophosphate; Drug: Rituximab; Drug: Busulfan; Drug: ATG; Drug: Cyclophosphamide; Drug: Mycophenolate mofetil; Drug: Tacrolimus

Interventions

Fludarabine monophosphate DRUG

180 mg/m2 over 6 days.

Hematopoietic Stem Cell Transplant

Rituximab DRUG

375 mg/m2 on day -13 and day -3

Also known as: Rituxan

Hematopoietic Stem Cell Transplant

Busulfan DRUG

AUC 1000-1200 microM.mt

Also known as: busulfex

Hematopoietic Stem Cell Transplant

ATG DRUG

2.5 mg/kg for 3 days

Also known as: Thymoglobulin

Hematopoietic Stem Cell Transplant

Cyclophosphamide DRUG

50 mg/kg on day +3

Also known as: Cytoxan

Hematopoietic Stem Cell Transplant

Mycophenolate mofetil DRUG

15 mg/kg q 8 hours

Also known as: MMF, Cell-cept.

Hematopoietic Stem Cell Transplant

Tacrolimus DRUG

0.03 mg/kg /d

Also known as: FK-506

Hematopoietic Stem Cell Transplant

Eligibility Criteria

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

You may qualify if:

• Patients must have sickle cell disease (genotype Hb SS or Sß° thalassemia), AND must have 1 or more of the following clinical complications related to Sickle cell disease:
• A clinically significant neurologic event (stroke) or any neurologic defect lasting \>24 hours, that is accompanied by an infarct on cerebral MRI.
• Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least 1 complete lung segment associated with acute symptoms including fever, chest pain, tachypnea, wheezing or cough) despite adequate supportive care measures (example: asthma therapy, hydroxyurea).
• History of severe pain episodes defined as 3 or more severe pain events per year in the 2 years prior to enrollment despite adequate supportive care measures and hydroxyurea trial (i.e. Hydroxyurea non-responders). Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than vaso-occlusion mediated by sickle cell disease.
• Recurrent priapism.
• Osteo-necrosis of multiple joints
• Evidence of Pulmonary Hypertension as evidenced by Tricuspid Regurgitation jet velocity (TRV) \> 2.5 m/s on Echocardiogram.
• Red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy.

You may not qualify if:

• Invasive bacterial, viral or fungal infections within 1 month prior to starting conditioning therapy.
• Female patients who are Pregnant (Beta HCG +) or breastfeeding.
• HIV positive patients.
• Patients with HLA-matched related family donors are not eligible for this study.
• Prior myeloablative allogeneic HCT.
• Patients on chronic transfusion therapy for ≥ 1 year with evidence of cirrhosis of liver on biopsy
• Any significant concurrent disease, illness, severe cognitive delay or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

fludarabine phosphate; Rituximab; Busulfan; thymoglobulin; Cyclophosphamide; Mycophenolic Acid; Tacrolimus

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Limitations and Caveats

No outcome data are available for this study as the study was terminated. The PI has left the institution and cannot be contacted.

Results Point of Contact

• Title: Kristy Ott
• Organization: Nationwide Children's Hospital

kristy.ott@nationwidechildrens.org

614-722-6313

Study Officials

• Sandeep Soni, MD

  Nationwide Children's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2011
• First Posted: January 19, 2011
• Study Start: September 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 3, 2019
• Results First Posted: April 3, 2019

Record last verified: 2019-04

Locations

US (1)