Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease

NCT ID: NCT01461837

Last Updated: 2025-08-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Sickle Cell Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Haplo Stem Cell Transplantation

CD34 selected T-cell depleted allogeneic SCT

Group Type EXPERIMENTAL

CD34 selected T-cell depleted allogeneic SCT

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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Familial haploidentical T-cell depleted allogeneic stem cell transplantation high risk Sickle Cell Disease

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role collaborator

Medical College of Wisconsin

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Tufts Medical Center

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role collaborator

Miltenyi Biomedicine GmbH

INDUSTRY

Sponsor Role collaborator

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role collaborator

New York Medical College

OTHER

Sponsor Role lead

Responsible Party

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Mitchell Cairo

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mitchell S Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Locations

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University of California Los Angeles (UCLA)

Los Angeles, California, United States

Site Status

Children's Hospital and Research Center Oakland

Oakland, California, United States

Site Status

Lurie Children's Hospital

Chicago, Illinois, United States

Site Status

Washington University/St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Medical College of Wisconsin/Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Braniecki S, Vichinsky E, Walters MC, Shenoy S, Shi Q, Moore TB, Talano JA, Parsons SK, Flower A, Panarella A, Fabricatore S, Morris E, Mahanti H, Milner J, McKinstry RC, Duncan CN, van de Ven C, Cairo MS. Neurocognitive outcome in children with sickle cell disease after myeloimmunoablative conditioning and haploidentical hematopoietic stem cell transplantation: a non-randomized clinical trial. Front Neurol. 2024 May 22;15:1263373. doi: 10.3389/fneur.2024.1263373. eCollection 2024.

Reference Type DERIVED
PMID: 38841694 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35110690 (View on PubMed)

Related Links

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http://www.sicklecelltransplantconsortium.org/

Consortium website for Parent-to-Child (haplo) Bone Marrow Transplant for Sickle Cell Disease (SCD)

Other Identifiers

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FD-R-0004090

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NYMC526-4090

Identifier Type: -

Identifier Source: org_study_id

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