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

Conditions

Sickle Cell Disease

Keywords

sickle cell disease, stem cell transplantation, haploidentical

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.

Hanif Mouehla, Marilyn J. Siegel, Edo Schaefer, Julie‐An Talano, Shalini Shenoy et al. (12 authors)

Blood2024-11-05

10.1182/blood-2024-208814

Neurocognitive outcome in children with sickle cell disease after myeloimmunoablative conditioning and haploidentical hematopoietic stem cell transplantation: a non-randomized clinical trial

Suzanne Braniecki, Elliott Vichinsky, Mark C. Walters, Shalini Shenoy, Qiuhu Shi et al. (18 authors)

Frontiers in Neurology2024-05-221 citations

10.3389/fneur.2024.1263373

Significant improvement of child physical and emotional functioning after familial haploidentical stem cell transplant.

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.

2022-02-023 citations

10.1038/s41409-022-01584-y

Elevated Pre-HSCT Ferritin is Not Associated with Increased Risk of Acute Graft Versus Host Disease in Patients with High Risk Sickle Cell Disease Undergoing Haploidentical T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT)

Yara Perez, Liana Klejmont, Harshini Mahanti, Jessica Hochberg, Allyson Flower et al. (11 authors)

Biology of Blood and Marrow Transplantation2018-02-03

10.1016/j.bbmt.2017.12.170

Treatment of High-Risk Sickle Cell Disease (SCD) with Familial Haploidentical (FHI) T-Cell Depleted (TCD) Stem Cell Transplantation with T-Cell Addback (IND 14359)

Cori Abikoff, Julie‐An Talano, Carolyn A. Keever-Taylor, Mark Walters, Shalini Shenoy et al. (21 authors)

Biology of Blood and Marrow Transplantation2015-01-221 citations

10.1016/j.bbmt.2014.11.110

Interventions

DRUGCD34 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

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 20 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Treatment related events	1 year	Death, primary or late graft rejection, or recurrence of disease and acceptable rate of hematopoietic engraftment, acute and chronic graft-versus-host disease

Secondary

Measure	Time frame	Description
neurological/neurocognitive status	2 years	Change from baseline in neurological/neurocognitive status
Pulmonary/pulmonary vascular status	2 years	Change from baseline of Pulmonary/pulmonary vascular status
Health-related quality of life	4 years	Change from baseline of Health-related quality of life (CHRIs-HSCT/CHRIs-General)

Countries

United States

Outcome results

None listed