ALS20-101 Lentiviral Gene Therapy for Beta Thalassemia

NCT06364774 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-020309
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this study is to find out if the blood disorder called transfusion-dependent beta thalassemia can be safely treated by modifying blood stem cells. This is done by collecting blood stem cells from the subject, modifying those cells, adding a healthy beta globin gene, and then giving them back to the subject. It is hoped that these modified cells will decrease the need for blood transfusions. The gene modified blood stem cells are called CHOP-ALS20 ("study drug"). This experimental gene therapy has not been tried on human beings before and is not FDA approved.

Conditions

Beta-Thalassemia

Keywords

Thalassemia; Beta Thalassemia; gene therapy; beta globin gene

Outcome Measures

Primary Outcomes (9)

• Neutrophil Engraftment

  time to neutrophil engraftment

  within 42 days after infusion

• Platelet Engraftment

  time to platelet engraftment

  through end of treatment, an average 1 year

• Overall Survival at 2 years

  Survival status after treatment ends

  2 years after treatment ends

• Incidence of transplant related mortality

  Incidence of transplant related mortality within 100 days and within 1 year after infusion

  1 year after infusion

• Incidence of Graft Versus Host Disease

  any clinical evidence of graft versus host disease (GVHD)

  through end of treatment, an average of 1 year

• Incidence of Vector-Derived Replication Competent Lentivirus

  The detection of vector-derived replication competent lentivirus in any subject throughout the study until end of treatment.

  through end of treatment, an average of 1 year

• Insertional Oncogenesis

  The number of subjects with insertional oncogenesis

  through the end of the study, up to 24 months

• Clonal Predominance

  The number of subjects with clonal predominance

  through the end of the study, up to 24 months

• maintain total hemoglobin level of 9.0 g/dL or higher

  The proportion of subjects able to discontinue regular red cell transfusions and maintain total hemoglobin level of 9.0 g/dL or higher (average over 1-year period) in the absence of red cell transfusion(transfusion independence). Success is defined as a minimum of 4 to 6 subjects achieving this endpoint.

  through the end of the study, up to 24 months

Study Arms (1)

beta thalassemia

EXPERIMENTAL

This arm will evaluate the safety and efficacy of infusing autologous hematopoietic stem and progenitor cells (HSPC) transduced with the novel lentiviral vector ALS20 that encodes the human βA-T87Q-globin gene, following myeloablative conditioning with busulfan.

Biological: ALS20

Interventions

ALS20 BIOLOGICAL

novel lentiviral vector ALS20

beta thalassemia

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to \< 40 years at the time of consent
• Diagnosis of transfusion dependent beta thalassemia (β0 β0, β+β0, β+β+, βEβ0, βEβ+,β0 or β+ /βA + alpha triplication(s)). Transfusion-dependent is defined as a history of receiving at least 120 mL/kg/year packed red blood cells or at least 8 transfusions per year in the past two years. The first 2 subjects enrolled must have a non- β0 β0 genotype.
• Genetic confirmation of α and β thalassemia diagnosis (β0β0, β+β0, β+β+, βEβ0, βEβ+, β0 or β+ /βA + alpha triplication(s)) by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory is required.
• Clinically stable, Karnofsky score at least 70, and eligible to undergo Hematopoietic Stem Cell Transplantation (HSCT).
• Female subjects of childbearing potential must agree to use acceptable method(s) of contraception from consent through at least 6 months after CHOP-ALS20 infusion
• Male subjects of reproductive capacity must agree to use effective contraception from start of mobilization through at least 6 months after CHOP-ALS20 infusion
• All potential treatment options including allogeneic HSCT (HLA-matched related, HLA-matched unrelated, and haploidentical) as well as FDA approved gene therapy options have been thoroughly discussed with the independent hematologist and/or transplant physician and subject agrees to proceed with this clinical trial.

You may not qualify if:

• Prior receipt of HSCT or gene therapy
• More than one alpha globin gene deletions/mutations.
• Any prior or current malignancy (excluding adequately treated basal or squamous cell carcinoma of the skin)
• Known cancer predisposition syndrome
• Positive for HIV-1, HIV-2, Human T Cell Lymphotropic Virus-1,2 (HTLV-1, HTLV-2) or active hepatitis B or active hepatitis C infection
• Clinically significant bleeding disorder
• Evidence of cardiac dysfunction (left ventricular ejection fraction \<50% or shortening fraction \<27%) or clinically significant arrhythmia
• Evidence of advanced liver disease (ALT \>5x the upper limit of normal (ULN), prothrombin time \>1.5 x ULN, direct bilirubin \> 3x ULN) not attributable to iron chelation therapy, or evidence of bridging fibrosis on liver biopsy or fibrosis stage of F3 or higher by magnetic resonance elastography (MRE) if obtained as part of clinical care
• Diffusion capacity of the lungs for carbon monoxide (DLco) \<50% of predicted (corrected for Hb)
• Pulse oximetry in room air \<92%
• Evidence of renal dysfunction (creatinine \>1.5x ULN or Glomerular Filtration Rate (GFR) \<70 ml/min/1.73 m2 based on cystatin C/creatinine equation)
• Cardiac T2 MRI \< 10 ms
• Platelet count \<100,000/mcL or absolute neutrophil count \<1000/mcL except if attributed to benign ethnic neutropenia
• Unable to receive red cell transfusion (significant allo/auto immunization)
• Uncontrolled systemic hypertension

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia

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

Study Officials

• Janet Kwiatkowski, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janet Kwiatkowski, MD

CONTACT

215-590-5286; kwiatkowski@chop.edu

Jaladhikumar Patel

CONTACT

267-426-5602; patelj23@chop.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

Model Details: Single arm pilot, phase I/II study of 12 subjects.

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: April 15, 2024
• Study Start: April 14, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)