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T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias

ConditionsSickle Cell AnemiaBeta-thalassemia MajorDiamond-blackfan Anemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age5-40
SponsorPaul Szabolcs

About this trial

The purpose of this study is to evaluate what effect, if any, mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant may have on severe sickle cell disease and other transfusion dependent anemias. By using mismatched unrelated volunteer donor and/or haploidentical related donor stem cells, this study will increase the number of patients who can undergo a stem cell transplant for their specified disease. Additionally, using a T-cell depleted approach should reduce the incidence of graft-versus-host disease which would otherwise be increased in a mismatched transplant setting.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patient, parent, or legal guardian must have given written informed consent and/or assent according to FDA guidelines.

Ages 5 years to 40 years, at time of consent.

Recurrent acute painful episodes (also known as vaso-occlusive crises; VOC) despite supportive care, minimum of 2 new pain events per year requiring hospitalization for parenteral pain management in the previous 2 years.

Recurrent acute chest syndrome (ACS) despite supportive care, minimum of 2 episodes in preceding 2-year period.

Disqualifiers

Patients with alternate, superior donor options (matched sibling donor or matched unrelated donor).

Patients who have undergone stem cell transplantation in the 6 months prior to anticipated conditioning.

Patients with history of a central nervous system (CNS) event within six months prior to start of conditioning (patient will be delayed until eligible).

Patients who are pregnant or lactating

Trial design

Design model

Single group

Treatments tested in this trial

  • CD3/CD19 depleted leukocytes

    Biological/Vaccine

    Negative selection for CD3+/CD19+ cells will be performed on the CliniMACS® depletion device.

  • CD45RA depleted leukocytes

    Biological/Vaccine

    Negative selection for CD45RA will be performed on the CliniMACS® depletion device.

  • Hydroxyurea

    Drug

    Sickle Cell Disease Conditioning

  • Rituximab

    Drug

    Sickle Cell Disease Conditioning

  • Alemtuzumab

    Drug

    Sickle Cell Disease Conditioning

  • Fludarabine

    Drug

    Sickle Cell Disease Conditioning

  • Thiotepa

    Drug

    Sickle Cell Disease Conditioning

Treatment groups

5 Participants
are divided into 1 treatment group
Group A: Hematopoietic Stem Cell TransplantationExperimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

Graft rejection

How frequent, if any, graft rejection occurs

Time frame
Day -30 through study completion, an average of 2 years
2

Post Transplant treatment related mortality

Number of deaths that occurred from treatment

Time frame
By day 100
3

Acute Graft versus host disease

The number of patients who develop acute graft versus host disease (GVHD)post transplant

Time frame
Day 0 through study completion, an average of 2 years
4

Chronic Graft versus host disease

The number of patients who develop chronic graft versus host disease (GVHD) post transplant

Time frame
Day 0 through study completion, an average of 2 years

Secondary outcomes

1

Neutrophil recovery

≥ 0.5 x 103/μL neutrophils for three consecutive days tested on different days.

Time frame
Day 0 through study completion, an average of 2 years
2

Donor Cell Engraftment

≥ 5% donor cells on day +42 and ≥ 10% donor cells on day +100. We will record if subjects have attained robust donor cell engraftment (\> 50% donor chimerism at 180 days).

Time frame
From Day 0, Day 42, Day 100 and Day 180. Further testing can be done if clinically indicated up to 2 years post transplant
3

Neurological complications

To evaluate the incidence of neurological complications

Time frame
Day 0 through study completion, an average of 2 years
4

Immune reconstitution

The pace of systemic immune reconstitution

Time frame
Day 0 through study completion, an average of 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Paul Szabolcs

Lead sponsor

University of Pittsburgh

Sponsor institution

Source ClinicalTrials.gov
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