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Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03121001
Recruitment Status : Recruiting
First Posted : April 19, 2017
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Damiano Rondelli, MD, University of Illinois at Chicago

Tracking Information
First Submitted Date  ICMJE April 14, 2017
First Posted Date  ICMJE April 19, 2017
Last Update Posted Date September 25, 2019
Actual Study Start Date  ICMJE March 20, 2017
Estimated Primary Completion Date September 12, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2017)
Estimate the number of patients who engraft by Day +60 [ Time Frame: Up to Day +60 ]
Patients who achieve < 5% peripheral blood donor chimerism by Day +30 and do not have a Day +60 measure will be regarded as failing to achieve full donor chimerism by Day +60; patients who achieve > 5% donor chimerism by Day +30 but do not have a Day +60 measure will be considered nonevaluable for the primary endpoint.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2017)
  • Disease free survival [ Time Frame: Up to Day +60 ]
    Using the Kaplan-Meier method, the probability of EFS will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive will also be estimated with a 90% exact binomial confidence interval. Cumulative incidences of transplant related mortality will be estimated separately using Grey's method.
  • Overall survival [ Time Frame: Up to Day +60 ]
    Using the Kaplan-Meier method, the probability of overall survival will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive will also be estimated with a 90% exact binomial confidence interval. Cumulative incidences of transplant related mortality will be estimated separately using Grey's method.
  • Adverse Effects [ Time Frame: Up to Day +60 ]
    The cumulative incidence of acute (grade II-IV, grade III-IV) and chronic GVHD will be estimated through competing-risk analysis using Grey's method, wherein graft failure, and death are competing risks for GVHD. Other selected toxicities (including rates of infection) will be reported descriptively.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
Official Title  ICMJE A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
Brief Summary

The study is a Phase II clinical trial. Patients will receive intensity modulated total body irradiation (TBI) at a dose of 3 Gy with standard fludarabine/ i.v. cyclophosphamide conditioning prior to human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplant (HSCT).

The primary objective of the study is to determine the engraftment at Day +60 following HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents and low-dose total body irradiation (TBI) for conditioning and post-transplant cyclophosphamide in patients with sickle cell disease.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Drug: ATG
    0.5 mg/kg IV on day -9, and 2 mg/kg on days -8 and day -7
    Other Name: Thymoglobulin®
  • Drug: fludarabine
    30 mg/m2 IVPB daily for day -6 (6 days before stem cell infusion) through day -2
  • Drug: cyclophosphamide
    14.5 mg/kg IV on days -6 and -5 and 50 mg/kg/d on days +3 and +4
  • Radiation: Total body irradiation
    3 Gy on day -1
  • Procedure: Stem cell infusion
    Stem cell product infused according to BMT unit policy on day 0.
  • Drug: Sirolimus
    loading dose of 15 mg followed by 5 mg per day on day +5
  • Drug: mycophenolate mofetil
    1 g every 8 h (until day 35) will be started on day 5
Study Arms  ICMJE Experimental: Subject treatment
Patients will receive the following conditioning regimen: ATG, fludarabine (6 days before stem cell infusion), cyclophosphamide, and total body irradiation. The stem cell product will be infused according to BMT unit policy. Patients will also receive GVHD prophylaxis which will consist of cyclophosphamide, sirolimus, and mycophenolate mofetil according to the protocol. Post-transplant evaluation will be done as per standard care with study data collected at days 30, 60, 100, 180, 365, and annually thereafter.
Interventions:
  • Drug: ATG
  • Drug: fludarabine
  • Drug: cyclophosphamide
  • Radiation: Total body irradiation
  • Procedure: Stem cell infusion
  • Drug: Sirolimus
  • Drug: mycophenolate mofetil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 14, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 12, 2024
Estimated Primary Completion Date September 12, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Patient Eligibility:

  1. Patients with sickle cell disease are eligible if they have any of the following complications:

    1.1 Stroke or central nervous system event lasting longer than 24 hours 1.2 Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, hospital admissions, or home bedrest leading to absence from work or school. 1.3 Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits 1.4 Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events 1.5 Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy 1.6 Bilateral proliferative retinopathy with major visual impairment in at least one eye 1.7 Osteonecrosis of 2 or more joints 1.8 Sickle cell nephropathy, defined by a GFR < 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin > 300 mg/g creatinine) 1.9 Pulmonary hypertension, defined by a mean pulmonary arterypressure >25mmHg

  2. Age 16-60 years
  3. Karnofsky performance status of 60 or higher (Appendix A)
  4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
  5. Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration)
  6. Estimated GFR ≥ 50mL/min/1.73m2 as calculated by the modified MDRD equation
  7. ALT ≤ 3x upper limit of normal
  8. HIV-negative
  9. Patient is not pregnant
  10. Patient is able and willing to sign informed consent
  11. Patient does not have a fully HLA-matched sibling donor
  12. Patient has an HLA-haploidentical relative

Donor Eligibility Relatives (parents, offspring, siblings, aunts/uncles, cousins) will be tested by molecular typing of HLA class I (A, B, and C) and class II (DRB1) at low resolution. Only those that are an HLA-haploidentical match (≥ 4/8) will be considered as a potential donor. NOTE: If during testing, a fully HLA-matched sibling donor is found and is willing to donate his/her stem cells, the potential subject will not be eligible for this protocol.

Donor consent will be obtained as per standard protocol of the bone marrow transplant unit.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Damiano Rondelli, MD 312 413-3547 drond@uic.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03121001
Other Study ID Numbers  ICMJE 2016-1152
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Damiano Rondelli, MD, University of Illinois at Chicago
Study Sponsor  ICMJE University of Illinois at Chicago
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Damiano Rondelli, MD University of Illinois at Chicago
PRS Account University of Illinois at Chicago
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP