Clinical trial NCT01461837: Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease
Official title: Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
stem cell transplantation
haploidentical
Lead sponsor: New York Medical College
Sponsor class: OTHER
Collaborators: name: UCSF Benioff Children's Hospital Oakland
name: Medical College of Wisconsin
name: Washington University School of Medicine
name: Tufts Medical Center
name: University of California, San Francisco
name: University of California, Los Angeles
name: Miltenyi Biomedicine GmbH
name: Ann & Robert H Lurie Children's Hospital of Chicago
First posted: 2011-10-28
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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 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.
  3. Recurrent painful events (at least 3 in the 2 years prior to enrollment).
  4. Abnormal TCD study requiring starting on chronic transfusion therapy.
  5. At least one silent infarct lesion on a MRI scan of the head.
* A familial haploidentical donor without homozygous sickle cell disease
* Adequate organ function (renal, liver, cardiac and pulmonary function)
* Karnofsky or Lansky (age appropriate) Performance Score ≥50%
* Liver biopsy is optional to assess for iron overload in chronically transfused patients.

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
* Karnofsky/Lansky (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

Primary outcomes:
measure: Treatment related events
timeFrame: 1 year
Secondary outcomes:
measure: neurological/neurocognitive status
timeFrame: 2 years
measure: Pulmonary/pulmonary vascular status
timeFrame: 2 years
measure: Health-related quality of life
timeFrame: 4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Saint Louis
country: United States
facility: Washington University/St. Louis Children's Hospital
state: Missouri
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: New York Medical College
name: Mitchell S Cairo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parsons SK, Rodday AM, Weidner RA, Morris E, Braniecki S, Shenoy S, Talano JA, Moore TB, Panarella A, Flower A, Milner J, Fabricatore S, Mahanti H, van de Ven C, Shi Q, Cairo MS. Significant improvement of child physical and emotional functioning after familial haploidentical stem cell transplant. Bone Marrow Transplant. 2022 Apr;57(4):586-592. doi: 10.1038/s41409-022-01584-y. Epub 2022 Feb 2.