A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Hematopoietic Stem Cell Transplant Stem cell infusion on Day 0. |
Drug: Fludarabine monophosphate
180 mg/m2 over 6 days.
Drug: Rituximab
375 mg/m2 on day -13 and day -3
Other Names:
Drug: Busulfan
AUC 1000-1200 microM.mt
Other Names:
Drug: ATG
2.5 mg/kg for 3 days
Other Names:
Drug: Cyclophosphamide
50 mg/kg on day +3
Other Names:
Drug: Mycophenolate mofetil
15 mg/kg q 8 hours
Other Names:
Drug: Tacrolimus
0.03 mg/kg /d
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Event-free Survival [1 year]
Event-free survival
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
Sponsors and Collaborators
- Nationwide Children's Hospital
Investigators
- Study Chair: Sandeep Soni, MD, Nationwide Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 09-00383
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Hematopoietic Stem Cell Transplant |
|---|---|
| Arm/Group Description | Drug: Fludarabine monophosphate 180 mg/m2 over 6 days. Drug: Rituximab 375 mg/m2 on day -13 and day -3 Other Names: •Rituxan Drug: Busulfan AUC 1000-1200 microM.mt Other Names: •busulfex Drug: ATG 2.5 mg/kg for 3 days Other Names: •Thymoglobulin Drug: Cyclophosphamide 50 mg/kg on day +3 Other Names: •Cytoxan Drug: Mycophenolate mofetil 15 mg/kg q 8 hours Other Names: •MMF, Cell-cept. Drug: Tacrolimus 0.03 mg/kg /d Other Names: •FK-506 |
| Period Title: Overall Study | |
| STARTED | 8 |
| COMPLETED | 1 |
| NOT COMPLETED | 7 |
Baseline Characteristics
| Arm/Group Title | Hematopoietic Stem Cell Transplant |
|---|---|
| Arm/Group Description | Stem cell infusion on Day 0. Fludarabine monophosphate: 180 mg/m2 over 6 days. Rituximab: 375 mg/m2 on day -13 and day -3 Busulfan: AUC 1000-1200 microM.mt ATG: 2.5 mg/kg for 3 days Cyclophosphamide: 50 mg/kg on day +3 Mycophenolate mofetil: 15 mg/kg q 8 hours Tacrolimus: 0.03 mg/kg /d |
| Overall Participants | 0 |
| Age () [] | |
| <=18 years | |
| Between 18 and 65 years | |
| >=65 years | |
| Age () [] | |
| Sex: Female, Male () [] | |
| Female | |
| Male | |
| Race and Ethnicity Not Collected () [] | |
| Region of Enrollment (participants) [] | |
| Study-Specific Measure () [] | |
Outcome Measures
| Title | Event-free Survival |
|---|---|
| Description | Event-free survival |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was terminated and the PI has left the institution. Efforts were made to contact the PI but unsuccessful. No outcome measure data is available for the study. |
| Arm/Group Title | HSCT Transplant |
|---|---|
| Arm/Group Description | HSCT transplant |
| Measure Participants | 0 |
Adverse Events
| Time Frame | From enrollment of first participation to study termination. | |
|---|---|---|
| Adverse Event Reporting Description | The study was terminated and the PI has left the institution. The only available information is in respect to the serious adverse events. | |
| Arm/Group Title | No Arm Analyzed: N/A | |
| Arm/Group Description | No outcome date are available for this study as the study was terminated. The PI has left the institution and cannot be contacted. | |
All Cause Mortality |
||
| No Arm Analyzed: N/A | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/0 (NaN) | |
Serious Adverse Events |
||
| No Arm Analyzed: N/A | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| No Arm Analyzed: N/A | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/0 (NaN) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Kristy Ott |
|---|---|
| Organization | Nationwide Children's Hospital |
| Phone | 614-722-6313 |
| kristy.ott@nationwidechildrens.org |
- 09-00383