Beta-ThalassemiaPhase 1/2NCT06364774
ALS20-101 Lentiviral Gene Therapy for Beta Thalassemia
A Phase 1/2 study testing ALS20 in people with Beta-Thalassemia, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Beta-Thalassemia
- What is being tested?
- ALS20
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Apr 2025to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 active bacterial, viral (including COVID-19 and influenza), fungal, or parasitic infection (temporary exclusion)
Show all 24Show fewer
- 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
- Liver R2 or R2 MRI or liver biopsy with liver iron concentration 15 mg/g dw (temporary exclusion)
- 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
- Uncontrolled seizure disorder
- Diagnosis of a significant psychiatric disorder that could seriously impede the ability to participate in the study as determined by the investigator
- Immediate family member with a known or suspected Familial Cancer Syndrome
- Contraindication to anesthesia
- For female subjects, pregnancy or breastfeeding
- Participation in another clinical trial of an investigational drug within 30 days or 5 drug half-lives, whichever is longer, of screening (temporary exclusion)
- Any other condition that would render the subject ineligible for mobilization/apheresis and/or HSCT as determined by the investigator
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 1/2 Study Evaluating the Safety and Efficacy of Gene Therapy Employing Lentiviral Vector ALS20-transduced Hematopoietic Progenitor Cells in Subjects With Transfusion-dependent-thalassemia
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.
Read the detailed description
Beta thalassemia major is a hereditary blood disorder that requires lifelong regular transfusions and is associated with significant morbidity, early mortality, and decreased quality of life. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited availability of suitable donors as well as risks of graft versus host disease limit its applicability. Gene addition of a functional beta globin gene may be an alternative treatment option.
The primary objective is to assess the safety of treatment with autologous hematopoietic stem cells transduced with a novel lentiviral vector (ALS20) in subjects 18 to <36 years old with transfusion dependent beta thalassemia.
The secondary objective is to evaluate the efficacy of treatment with autologous hematopoietic stem cells transduced with a novel lentiviral vector (ALS20) in subjects 18 to < 36 years old with transfusion dependent beta thalassemia.
Study Design: This is a single arm pilot, phase 1/2 study of up to 12 subjects ages 18 to <36 years who have transfusion-dependent beta thalassemia (genotypes β0β0, β+β0, β+β+, βEβ0, βEβ+, dominant β thalassemia). The study 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, following myeloablative conditioning with busulfan.
The main risks of this study involve risks of the genetic modification of the stem cells and the busulfan chemotherapy conditioning. Genetic modification of blood stem cells may increase the risk of blood cancer. The main risks of busulfan conditioning include prolonged low blood counts, liver injury, infertility, and cancer. There also is a risk of failure of the modified blood stem cells to grow.
- Conditions
- Beta-Thalassemia
- Being tested
- ALS20
- Keywords
- Thalassemia, Beta Thalassemia, gene therapy, beta globin gene
- Medical subject headings
- beta-Thalassemia, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALS20Biological
novel lentiviral vector ALS20
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: ALS20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutrophil Engraftment
time to neutrophil engraftment
Measured: within 42 days after infusion
Platelet Engraftment
time to platelet engraftment
Measured: through end of treatment, an average 1 year
Overall Survival at 2 years
Survival status after treatment ends
Measured: 2 years after treatment ends
Incidence of transplant related mortality
Incidence of transplant related mortality within 100 days and within 1 year after infusion
Measured: 1 year after infusion
Incidence of Graft Versus Host Disease
any clinical evidence of graft versus host disease (GVHD)
Measured: 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.
Measured: through end of treatment, an average of 1 year
Insertional Oncogenesis
The number of subjects with insertional oncogenesis
Measured: through the end of the study, up to 24 months
Clonal Predominance
The number of subjects with clonal predominance
Measured: 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.
Measured: through the end of the study, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2024
- Study start14 Apr 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Beta-ThalassemiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm pilot, phase I/II study of 12 subjects.
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Janet Kwiatkowski, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06364774
- Sponsor's protocol ID
- 22-020309
- Status last verified
- Oct 2026
- First submitted
- 26 Mar 2024
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study Evaluating the Safety and Efficacy of Gene Therapy Employing Lentiviral Vector ALS20-transduced Hematopoietic Progenitor Cells in Subjects With Transfusion-dependent-thalassemia
- ClinicalTrials.gov ID
- NCT06364774
- Acronym / sponsor ID
- 22-020309
- Conditions
- Beta-Thalassemia
- Keywords
- Thalassemia, Beta Thalassemia, gene therapy, beta globin gene
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- 14 Apr 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 15 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Beta thalassemia major is a hereditary blood disorder that requires lifelong regular transfusions and is associated with significant morbidity, early mortality, and decreased quality of life. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited availability of suitable donors as well as risks of graft versus host disease limit its applicability. Gene addition of a functional beta globin gene may be an alternative treatment option.
The primary objective is to assess the safety of treatment with autologous hematopoietic stem cells transduced with a novel lentiviral vector (ALS20) in subjects 18 to <36 years old with transfusion dependent beta thalassemia.
The secondary objective is to evaluate the efficacy of treatment with autologous hematopoietic stem cells transduced with a novel lentiviral vector (ALS20) in subjects 18 to < 36 years old with transfusion dependent beta thalassemia.
Study Design: This is a single arm pilot, phase 1/2 study of up to 12 subjects ages 18 to <36 years who have transfusion-dependent beta thalassemia (genotypes β0β0, β+β0, β+β+, βEβ0, βEβ+, dominant β thalassemia). The study 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, following myeloablative conditioning with busulfan.
The main risks of this study involve risks of the genetic modification of the stem cells and the busulfan chemotherapy conditioning. Genetic modification of blood stem cells may increase the risk of blood cancer. The main risks of busulfan conditioning include prolonged low blood counts, liver injury, infertility, and cancer. There also is a risk of failure of the modified blood stem cells to grow.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm pilot, phase I/II study of 12 subjects.
| Arm | Type | Receives |
|---|---|---|
| beta thalassemia | Experimental | Biological: ALS20This 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALS20novel lentiviral vector ALS20 | Biological | beta thalassemia |
Primary outcome
Neutrophil Engraftment
Time frame: within 42 days after infusion
time to neutrophil engraftment
Platelet Engraftment
Time frame: through end of treatment, an average 1 year
time to platelet engraftment
Overall Survival at 2 years
Time frame: 2 years after treatment ends
Survival status after treatment ends
Incidence of transplant related mortality
Time frame: 1 year after infusion
Incidence of transplant related mortality within 100 days and within 1 year after infusion
Incidence of Graft Versus Host Disease
Time frame: through end of treatment, an average of 1 year
any clinical evidence of graft versus host disease (GVHD)
Incidence of Vector-Derived Replication Competent Lentivirus
Time frame: through end of treatment, an average of 1 year
The detection of vector-derived replication competent lentivirus in any subject throughout the study until end of treatment.
Insertional Oncogenesis
Time frame: through the end of the study, up to 24 months
The number of subjects with insertional oncogenesis
Clonal Predominance
Time frame: through the end of the study, up to 24 months
The number of subjects with clonal predominance
maintain total hemoglobin level of 9.0 g/dL or higher
Time frame: through the end of the study, up to 24 months
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Beta-Thalassemia
Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia
RecruitingObservational study
Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy
Transfusion-dependent Beta-Thalassemia, Gene Therapy
Not yet recruiting
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Beta-Thalassemia
RecruitingPhase 1/2
β-Thalassemia Treatment With KL003 Cell Injection
Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 3
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet Kwiatkowski, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ALS20 in people with Beta-Thalassemia, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neutrophil Engraftment (time frame: within 42 days after infusion). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.