Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (HaploSCD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by New York Medical College
Sponsor:
Collaborators:
Children's Hospital & Research Center Oakland
Medical College of Wisconsin
Washington University Early Recognition Center
Tufts Medical Center
University of California, San Francisco
University of California, Los Angeles
Miltenyi Biotec GmbH
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College
ClinicalTrials.gov Identifier:
NCT01461837
First received: October 19, 2011
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This study is being done to determine the safety and outcome (long-term control) of a high-dose chemotherapy regimen followed by an infusion of CD34 selected (immune cells) stem cells from a partially matched adult family member donor, called haploidentical stem cell transplantation, in high-risk sickle cell disease patients.

Funding Source - FDA OOPD


Condition Intervention Phase
Sickle Cell Disease
Drug: CD34 selected T-cell depleted allogeneic SCT
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)

Resource links provided by NLM:


Further study details as provided by New York Medical College:

Primary Outcome Measures:
  • Treatment related events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Death, primary or late graft rejection, or recurrence of disease and acceptable rate of hematopoietic engraftment, acute and chronic graft-versus-host disease


Secondary Outcome Measures:
  • neurological/neurocognitive status [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Change from baseline in neurological/neurocognitive status

  • Pulmonary/pulmonary vascular status [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Change from baseline of Pulmonary/pulmonary vascular status

  • Health-related quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Change from baseline of Health-related quality of life


Estimated Enrollment: 35
Study Start Date: January 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Haplo Stem Cell Transplantation
CD34 selected T-cell depleted allogeneic SCT
Drug: CD34 selected T-cell depleted allogeneic SCT
Hydroxyurea (60 mg/kg/day) and azathioprine (3 mg/kg/day) day -59 to day -11; fludarabine (30 mg/m2) Days -17, -16, -15, -14, -13; busulfan (3.2 mg/kg/day) Days -12, -11, -10, -9; thiotepa (10 mg/kg IV) day -8; cyclophosphamide (50 mg/kg) Days -7, -6, -5, -4; TLI on day -3; rabbit ATG (2.0 mg/kg/day) day -5,-4,-3, and -2; Stem Cell infusion day 0
Other Names:
  • Familial haploidentical
  • T-cell depleted
  • allogeneic stem cell transplantation
  • high risk Sickle Cell Disease

Detailed Description:

The purpose of this study is to investigate host myeloimmunosuppressive conditioning followed by familial haploidentical T cell depleted allogeneic stem cell transplantation in patients with high risk Sickle Cell Disease (SCD). It is hypothesized that it will be safe and well tolerated, and result in sustained donor chimerism, acceptable engraftment and immune reconstitution. Also, that it will limit SCD related organ damage resulting in improved and/or stable neurological, neurocognitive, pulmonary and pulmonary vascular function and health related quality of life (QOL).

Patients 2-20.99 years of age with a diagnosis of high-risk SCD and with an unaffected HLA partially matched family donor and meeting eligibility criteria (inclusion and exclusion criteria) are eligible.

  Eligibility

Ages Eligible for Study:   2 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous Hemoglobin S Disease, or Hemoglobin S Beta0/+ thalassemia
  • Patients must demonstrate one or more of the following Sickle Cell Disease Complications

    1. Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
    2. Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least one complete lung segment associated with acute symptoms including fever >38.5, chest pain, tachypnea, intercostal retractions, nasal flaring, use of accessory muscles of respiration, wheezing, rales, or cough not attributable to asthma or bronchiolitis) in the preceding two year period prior to enrollment that have failed, been non-compliant or declined hydroxyurea treatment,. The acute chest syndrome event occurred despite adequate supportive care measures (i.e. despite the use of supportive care and interventions including asthma therapy and/or hydroxyurea; patients who decline hydroxyurea or non-compliant with this therapy are eligible if they meet the other pulmonary criteria defined above for inclusion).
    3. Recurrent painful events (at least 3 in the 2 years prior to enrollment). Pain occurred in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than sickle cell disease. Pain lasted at least 2-4 hours and required parenteral narcotic treatment, or an equianalgesic dose of oral narcotics or parenteral nonsteroidal anti-inflammatory drugs. These painful events may have been treated in any setting; however, the events, including events that were managed at home, will be considered for eligibility only if there is documentation of the event in a clinical record that may be reviewed by the investigator.
    4. Abnormal TCD study requiring starting on chronic transfusion therapy.
  • A familial haploidentical donor without homozygous sickle cell disease
  • Serum creatinine ≤1.5 x upper limit of normal for age and Creatinine clearance >60 ml/min/m2 or radioisotope GFR >100 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
  • Direct bilirubin <2.0 x upper limit of normal for age as per local laboratory OR AST or ALT <5.0 x upper limit of normal as per local laboratory
  • Shortening fraction ≥27% by echocardiogram or Ejection fraction of >40% by echocardiogram
  • Pulse oximetry ≥85% on room air, and DLCO ≥50% (corrected for hemoglobin) in cooperative patients in whom pulmonary function testing can be performed.
  • Karnofsky or Lansky (age appropriate) Performance Score ≥50%
  • For all patients receiving chronic transfusions for ≥1 year and a serum ferritin >1000 ng/ml, a liver biopsy will be performed to assess for iron overload.

Exclusion Criteria:

  • Females who are pregnant or breast-feeding
  • SCD Patients with documented uncontrolled infection
  • SCD patients who have an unaffected HLA matched family donor willing to proceed to donation or a willing and acceptable 8/8 matched unrelated donor eligible for the BMT/CTN SCURT trial
  • KarnofskyLansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
  • Demonstrated lack of compliance with medical care.
  • Clinically significant fibrosis or cirrhosis of the liver
  • Previously received a HSCT
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01461837

Contacts
Contact: Mitchell S Cairo, MD 914-594-2150 mitchell_cairo@nymc.edu
Contact: Erin Morris, RN 714-964-5359 erin_morris@nymc.edu

Locations
United States, California
University of California Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Theodore Moore, MD    310-825-6708    tbmoore@mednet.ucla.edu   
Contact: LaMarr Taylor, CCRP    310-794-8929    LaMarrTaylor@mednet.ucla.edu   
Principal Investigator: Theodore Moore, MD         
Children's Hospital and Research Center Oakland Recruiting
Oakland, California, United States, 94609
Contact: Mark Walters, MD    510-428-3374    MWalters@mail.cho.org   
Contact: Cyrus Bascon       cbascon@mail.cho.org   
Principal Investigator: Mark Walters, MD         
United States, Missouri
Washington University/St. Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Shalini Shenoy, MD    314-454-6018    Shenoy@kids.wustl.edu   
Contact: Megan Holtmann    314-454-6018      
Principal Investigator: Shalini Shenoy, MD         
United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell S Cairo, MD    914-594-2150    mitchell_cairo@nymc.edu   
Contact: Sandi Foley, RN, PNP    914-594-2152    Foleys@wcmc.com   
Principal Investigator: Mitchell S Cairo, MD         
United States, Wisconsin
Medical College of Wisconsin/Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Julie Talano, MD    414-955-4185    jtalano@mcw.edu   
Contact: Kathy Jodarski    414-266-2681    kjodarski@chw.org   
Principal Investigator: Julie Talano, MD         
Sponsors and Collaborators
New York Medical College
Children's Hospital & Research Center Oakland
Medical College of Wisconsin
Washington University Early Recognition Center
Tufts Medical Center
University of California, San Francisco
University of California, Los Angeles
Miltenyi Biotec GmbH
Investigators
Principal Investigator: Mitchell S Cairo, MD New York Medical College
  More Information

Additional Information:
No publications provided

Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT01461837     History of Changes
Other Study ID Numbers: NYMC526-4090, FD-R-0004090
Study First Received: October 19, 2011
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York Medical College:
sickle cell disease
stem cell transplantation
haploidentical

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 22, 2014