Recruiting NCT04819841
Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: nula-cel Drug Product.
- Who it may be relevant to
- Registry conditions: Sickle Cell Disease. Basic parameters: 12 years — 50 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase I/II Study of Nula-cel in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease
Overview
This study is a first-in-human, single-arm, open-label Phase I/II study of nula-cel in approximately 15 participants, diagnosed with severe Sickle Cell Disease. The primary objective is to evaluate safety of the treatment in this patient population, as well as preliminary efficacy and pharmacodynamic data.
Detailed description
Participants diagnosed with severe SCD will receive nula-cel via IV infusion following myeloablative conditioning in an autologous HSCT setting.
Interventions
- Genetic nula-cel Drug Product
nula-cel is administered via IV infusion following a myeloablative conditioning regimen
Primary outcome measures
- Proportion of patients who reach neutrophil engraftment [Time frame: 42 days post-infusion]
- Incidence rate of treatment-related mortality [Time frame: 100 days post-infusion]
- Incidence rate of treatment-related mortality [Time frame: 12 months post-infusion]
- Overall survival [Time frame: 24 months post-infusion]
- Frequency and severity of AEs/SAEs [Time frame: 24 months post-infusion]
Secondary outcome measures (11)
- Time to neutrophil engraftment [Time frame: through study completion, up to 24 months post-infusion]
- Time to platelet engraftment [Time frame: through study completion, up to 24 months post-infusion]
- Evaluation of gene correction levels in peripheral myeloid cells [Time frame: through study completion, up to 24 months post-infusion]
- Evaluation of adult Hgb as a percentage of total Hgb [Time frame: through study completion, up to 24 months post-infusion]
- Evaluation of HbS as a percentage of total Hgb [Time frame: through study completion, up to 24 months post-infusion]
- Total Hgb without disease-indicated transfusion support [Time frame: through study completion, up to 24 months post-infusion]
- Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications [Time frame: through study completion, up to 24 months post-infusion]
- Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs) [Time frame: over time, from 6 months to 18 months post-infusion]
- Incidence rate of any sVOCs [Time frame: over time, from 6 months to study completion, up to 24 months post-infusion]
- Proportion of participants achieving HbS <50% for at least 3 months [Time frame: through study completion, up to 24 months post-infusion]
- Evaluation of globin chain expression compared to baseline [Time frame: through study completion, up to 24 months post-infusion]
Eligibility criteria
Inclusion criteria
- ≥12 to ≤ 40 years
- Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:
- recurrent severe VOC (≥ 4 episodes in the preceding 2 years)
- ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)
- Lansky/Karnofsky performance status of ≥ 80
Exclusion criteria
- Available 10/10 HLA-matched sibling donor
- Prior HSCT or gene therapy
- Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder
- Clinically significant and active bacterial, viral, fungal or parasitic infection
- Pregnancy or breastfeeding in a postpartum female
- Presence of a chromosomal abnormality/mutation that may put the participant at an increased risk for MDS or AML per investigator's judgment
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 6 centers
- Children's Hospital Los Angeles — Los Angeles
- Lucile Packard Children's Hospital — Palo Alto
- Washington University — St Louis
- Columbia University Irving Medical Center — New York
- Memorial Sloan Kettering — New York
- Nationwide Children's Hospital — Columbus
Identifiers
NCT: NCT04819841 · KMAU-001-001