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

Primary Purpose

Sickle Cell Disease

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fludarabine monophosphate

Rituximab

Busulfan

ATG

Cyclophosphamide

Mycophenolate mofetil

Tacrolimus

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell, stem cell transplant

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Nationwide Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hematopoietic Stem Cell Transplant

Arm Description

Stem cell infusion on Day 0.

Outcomes

Primary Outcome Measures

Event-free Survival

Event-free survival

Secondary Outcome Measures

Full Information

NCT ID

NCT01279616

First Posted

January 18, 2011

Last Updated

April 2, 2019

Sponsor

Nationwide Children's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01279616

Brief Title

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

Official Title

A Pilot Study of an Immunosuppressive and Myeloablative Preparative Regimen for Allogeneic Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Severe Sickle Cell Disease

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Terminated

Why Stopped

PI moving to a different institution.

Study Start Date

September 2010 (Actual)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nationwide Children's Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

The primary goal of this pilot study is to determine the safety and feasibility of the preparative regimen for HSCT using a novel reduced toxicity regimen for stem cell transplant with unrelated donors. Analysis will be geared to confirm if the study regimen, followed by an appropriately HLA-matched unrelated donor (MUD)or unrelated cord blood HSCT, can lead to durable donor engraftment with reasonable toxicity, inhibiting sickle erythropoiesis and limiting disease related organ toxicity in patients who are at high risk for morbidity and mortality associated with sickle cell disease (SCD).

6. Conditions and Keywords

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

Sickle Cell Disease

Keywords

sickle cell, stem cell transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hematopoietic Stem Cell Transplant

Arm Type

Experimental

Arm Description

Stem cell infusion on Day 0.

Intervention Type

Drug

Intervention Name(s)

Fludarabine monophosphate

Intervention Description

180 mg/m2 over 6 days.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Busulfan

Other Intervention Name(s)

busulfex

Intervention Description

AUC 1000-1200 microM.mt

Intervention Type

Drug

Intervention Name(s)

ATG

Other Intervention Name(s)

Thymoglobulin

Intervention Description

2.5 mg/kg for 3 days

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

50 mg/kg on day +3

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil

Other Intervention Name(s)

MMF, Cell-cept.

Intervention Description

15 mg/kg q 8 hours

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

FK-506

Intervention Description

0.03 mg/kg /d

Primary Outcome Measure Information:

Title

Event-free Survival

Description

Event-free survival

Time Frame

1 year

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sandeep Soni, MD

Organizational Affiliation

Nationwide Children's Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Nationwide Children's Hospital

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43205

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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