Haploidentical Transplantation With Pre-Transplant Immunosuppressive Therapy for Patients With Sickle Cell Disease

NCT03279094 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17182
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease. The overall goal of this study is to expand the donor pool for hematopoietic stem cell transplantation in sickle cell disease using haploidentical donors, and to develop a non-toxic, myeloablative regimen, with the goal of achieving a consistent donor chimerism utilizing pre-transplant immunosuppressive therapy.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Hematopoietic stem cell transplantation; Haploidentical stem cell transplantation; Post-transplant Cytoxan

Outcome Measures

Primary Outcomes (1)

• Rate of unacceptable adverse events that are defined as any of the following events that occur from start of pre-transplant immunosuppressive therapy to the first 100 days post HCT:

  * Rate of death of any causes * Rate of study discontinuation or early withdrawal * Rate of graft failure • Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve \<30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft. * Rate of grade 4 non-hematological toxicities per NCI CTCAE v4.03 that last more than 21 days

  190 days

Secondary Outcomes (12)

• Time to donor neutrophil engraftment

  24 months

• Time to donor platelets engraftment

  24 months

• Rate of graft failure

  24 months

• Incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation

  100 days after transplantation

• Incidence of chronic GvHD

  24 months

Study Arms (1)

Haploidentical stem cell transplantation

EXPERIMENTAL

Biological: Hematopoietic stem cell transplantation

Interventions

Hematopoietic stem cell transplantation BIOLOGICAL

Haploidentical stem cell transplantation with pre-transplant immunosuppressive therapy

Haploidentical stem cell transplantation

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: Patients with sickle cell anemia (Hgb SS or SB° Thalassemia) with baseline Hgb S more than 60%.
• Disease status:
• Significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours; or increased transcranial Doppler velocity (\>200 m/s).
• History of one or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea).
• History of one or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).
• Recurrent priapism requiring medical therapy.
• Osteonecrosis of two or more joints despite the institution of supportive care measures.
• Prior treatment with regular RBC transfusion therapy, defined as receiving 8 or more transfusions per year for \> 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
• Echocardiograph finding of tricuspid valve regurgitation jet (TRJ) velocity ≥ 2.5 m/sec.
• Ages 1 to 30.
• Child Bearing Potential- Transplantation could be teratogenic and/or lethal to the developing fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
• Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.
• The recipient must have a related donor who is genotypically haploidentical on HLA-A, B, C and DRB1 loci.
• No HLA matched sibling or 10/10 matched unrelated donor is available.

You may not qualify if:

• Any uncontrolled illness including ongoing or active bacterial, viral or fungal infection.
• Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any in the pre- or post-transplant regimen.
• Pregnant women are excluded from this study.
• Patients with any active malignancy are ineligible for this study, other than non-melanoma skin cancers.
• Medical problem or neurologic/psychiatric dysfunction which would impair patient ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the principal investigator would place the recipient at unacceptable risk.
• Prior autologous or allogeneic transplant.
• Fully HLA-matched related or unrelated donor is available to donate.
• Non-Compliance: Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Anna B. Pawlowska, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2017
• First Posted: September 12, 2017
• Study Start: February 2, 2018
• Primary Completion (Estimated): January 25, 2027
• Study Completion (Estimated): January 25, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)