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

NCT03653338 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY19050050
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickle Cell Anemia; Beta-thalassemia Major; Diamond-blackfan Anemia

Keywords

Sickle Cell; Diamond-Blackfan; Beta-thalassemia; Anemia; Stem cell transplantation; Unrelated Donor; haploidentical; hematopoietic stem cell transplant (HSCT); bone marrow transplant (BMT); mismatched; t-cell depletion

Outcome Measures

Primary Outcomes (6)

• Graft rejection

  How frequent, if any, graft rejection occurs

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

• Post Transplant treatment related mortality

  Number of deaths that occurred from treatment

  By day 100

• Acute Graft versus host disease

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

  Day 0 through study completion, an average of 2 years

• Chronic Graft versus host disease

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

  Day 0 through study completion, an average of 2 years

• Post Transplant treatment related mortality

  Number of deaths that occurred from treatment

  Day 180

• Post Transplant treatment related mortality

  Number of deaths that occurred from treatment

  1 year

Secondary Outcomes (14)

• Neutrophil recovery

  Day 0 through study completion, an average of 2 years

• Donor Cell Engraftment

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

• Neurological complications

  Day 0 through study completion, an average of 2 years

• Immune reconstitution

  Day 0 through study completion, an average of 2 years

• Cytomegalovirus (CMV) infection

  Day 0 through study completion, an average of 2 years

Study Arms (1)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

All patients will receive a CD3+/CD19+ depleted stem cell transplant. In this study, the investigators will use HLA mismatched unrelated or haploidentical related donor peripheral blood stem cells. Prior to transplantation, the marrow (90-95%) will be negatively selected for CD3/CD19 using the ClinicMACs® depletion device. The remaining (5-10%) will undergo CD45+RA+ depletion and be frozen for future use as an immune boost. Subjects will undergo hematopoietic stem cell transplant utilizing CD3+/CD19+ depleted cells following conditioning therapy.

Biological: CD3/CD19 depleted leukocytes; Biological: CD45RA depleted leukocytes; Drug: Hydroxyurea; Drug: Rituximab; Drug: Alemtuzumab; Drug: Fludarabine; Drug: Thiotepa

Interventions

CD3/CD19 depleted leukocytes BIOLOGICAL

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

Hematopoietic Stem Cell Transplantation

CD45RA depleted leukocytes BIOLOGICAL

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

Hematopoietic Stem Cell Transplantation

Hydroxyurea DRUG

Sickle Cell Disease Conditioning

Also known as: HU, Hydrea

Hematopoietic Stem Cell Transplantation

Rituximab DRUG

Sickle Cell Disease Conditioning

Also known as: Rituxan

Hematopoietic Stem Cell Transplantation

Alemtuzumab DRUG

Sickle Cell Disease Conditioning

Also known as: Campath-1H

Hematopoietic Stem Cell Transplantation

Fludarabine DRUG

Sickle Cell Disease Conditioning

Also known as: Fludara

Hematopoietic Stem Cell Transplantation

Thiotepa DRUG

Sickle Cell Disease Conditioning

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 5 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Diagnosis of Sickle Cell Disease (Hemoglobin SS, Sβ0-thalassemia) complicated by any of the following:
• 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.
• Stroke or neurologic event lasting \> 24 hours with an accompanying infarct on MRI in any patient for all ages; Brain MRI with silent infarct without clinical event in patients ≤ 16 years.
• Chronic transfusion therapy defined as \> 8 packed red blood cell transfusions per year in the year prior to enrollment and/or evidence of red blood cell alloimmunization.
• Elevated transcranial Doppler velocities - \> 200 cm/s, via the non-imaging technique or \> 185 cm/s by the imaging technique measured on 2 separate occasions ≥ 1-month apart
• Elevated TRV \> 2.6m/s in patients ≥ 16 years old.
• Sickle-related renal insufficiency and/or sickle hepatopathy and/or any irreversible end-organ damage in patients ≥ 16 years old.
• OR Diagnosis of beta-thalassemia or Diamond-Blackfan anemia complicated by transfusion dependence with evidence of iron overload.
• A minimum donor match of 4/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1 loci in the related setting or minimum donor match of 6/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1 loci (with the DRB1 locus as a full match requirement). An unrelated donor and cord blood search must have been completed without an eligible 8/8 matched unrelated donor or 6/8 cord blood unit available. Patients who may have acceptable cord blood donor options (4/6 or better) but are limited by cell dose of a single cord will also be eligible for the proposed study.
• Adequate function of other organ systems as measured by:
• Creatinine clearance or GFR ≥ 45 ml/min/1.73m.
• Hepatic transaminases (ALT/AST) ≤ 3 x upper limit of normal.

You may not qualify if:

• 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
• Patients with uncontrolled bacterial, viral or fungal infection
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia; Anemia, Diamond-Blackfan; Anemia

Interventions

Hydroxyurea; Rituximab; Alemtuzumab; fludarabine; fludarabine phosphate; Thiotepa

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Paul Szabolcs, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Szabolcs, MD

CONTACT

412-692-6225; paul.szabolcs@chp.edu

Shawna McIntyre, RN

CONTACT

412-692-5552; mcintyresm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Blood and Marrow Transplantation and Cellular Therapy

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 31, 2018
• Study Start: August 2, 2018
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)