US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease
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|ClinicalTrials.gov Identifier: NCT04594031|
Recruitment Status : Recruiting
First Posted : October 20, 2020
Last Update Posted : July 19, 2021
The application of experimental hematopoietic cell transplantation (HCT) therapy in sickle-cell disease (SCD) must strike a balance between the underlying disease severity and the possibility of a direct benefit of the treatment, particularly in pediatric populations. Clinical studies in adults with SCD have focused on interventions that prolong survival and improve the quality of life. Unlike children, adults with SCD are much more likely to have a debilitating complication. As a result, the risk/benefit ratio of HCT is very favorable in adults, particularly if an approach to HCT that defines an acceptable level of toxicity can be established.
Whereas hematopoietic stem cell transplantation (HSCT) remains the only curative treatment currently available for patients with SCD, the morbidity, the frequent irreversible damage in target organs and the mortality reported in the natural course of patients with severe SCD are strong incentives to perform HSCTs in younger age groups. For those who lack a matched related donor, CB transplant is an appealing option, but despite been less problematic, CB accessibility related to cell dose of appropriately matched cord blood unit (CBU) remains a significant issue. Through a 7-day culture process of a CBU's hematopoietic stem cell HSCs with the UM171 compound, the total cell dose is increased mitigating this limitation.
UM171-CB expansion (ECT-001-CB) allows a greater CB accessibility, the selection of better matched cords that might translate into favourable clinical outcomes as reported in previous trials, including a lower risk of graft-versus-host disease. After CB selection and ex-vivo expansion, ECT-001-CB transplant will follow a myeloablative reduced-toxicity conditioning regimen consisting of rATG, busulfan and fludarabine with doses of all agents optimized to the individual using model-based dosing and will be followed by standard supportive care and GVHD prophylaxis consisting of tacrolimus and MMF.
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease Umbilical Cord Blood Hematopoietic Cell Proliferation||Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Multicenter Study of Hematopoietic Stem Cell Transplant of ECT-001-Expanded Cord Blood With a Reduced Toxicity Conditioning Regimen in Patients With Severe Sickle Cell Disease|
|Actual Study Start Date :||July 13, 2021|
|Estimated Primary Completion Date :||September 1, 2023|
|Estimated Study Completion Date :||February 2, 2024|
Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)
Single ECT-001-CB transplant (CD34+: 2 to 5.75x10E5/kg, CD3+ >1x10E6/kg)
- Evaluate feasibility of finding a suitable ECT-001-CB graft for transplantation in the context of SCD. [ Time Frame: Up to 24-months ]Calculate the proportion of recruited SCD patients for whom a suitable CBU (i.e., ≥ 6/8 human leukocyte antigen (HLA) with an appropriate cell dose) is identified.
- Evaluate feasibility of a successfully performing ECT-001-CB transplantation in the context of SCD. [ Time Frame: During accrual (up to 24-months) ]Calculate the percentage of selected grafts that will be successfully expanded and transplanted with absence of technical hurdles
- Evaluate the Safety of ECT-001-CB by evaluating tri-lineage hematopoietic reconstitution [ Time Frame: Up to 12-Months ]Measure the time required to achieve neutrophil and platelet engraftment
- Evaluate the Safety of ECT-001-CB by calculating incidence of acute and chronic GvHD [ Time Frame: Up to 12-Months ]Calculate incidence of Acute GVHD and Chronic GVHD as per NIH criteria
- Evaluate the Safety of ECT-001-CB by evaluating adverse events [ Time Frame: Up to 12-Months ]Calculate the Incidence of Adverse Events from the beginning of the conditioning regimen up to 12 months after ECT-001-CB transplant
- Evaluate the Safety of ECT-001-CB by evaluating incidence of transplant related mortality (TRM) [ Time Frame: Up to 12-Months ]Calculate incidence of any mortality related to the investigational product until the end of evaluation period.
- Evaluate the Safety of ECT-001-CB by incidence of graft failure [ Time Frame: Up to 100 days ]Calculate the incidence of primary and late graft failure
- Determine the pharmacologic effect of ECT-001-CB by evaluating donor chimerism [ Time Frame: Up to 12-Months post treatment ]The percentage of hematopoietic chimerism, based on DNA polymorphisms, will be measured and compared to baseline.
- Determine the pharmacologic effect of ECT-001-CB by measuring sickle hemoglobin (HbS) in peripheral blood. [ Time Frame: Up to 12-Months post treatment ]The concentration of the Sickle Hemoglobin (HbS) will be compared to baseline.
- Evaluate impact of ECT-001-CB on SCD-related events during the study period. [ Time Frame: Up to 12-Months post treatment ]The incidence of SCD-related adverse events will be compared to internal controls
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04594031
|Contact: Study Manageremail@example.com|
|Contact: Back-up Contactfirstname.lastname@example.org|
|United States, California|
|Stanford University School of Medicine||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: David Shyr, MD email@example.com|
|Sub-Investigator: Alice Bertaina, MD|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94158|
|Contact: Sandhya Kharbanda, MD Sandhya.firstname.lastname@example.org|
|Sub-Investigator: Janel Long Boyle, PhD|
|Study Director:||Medical Monitor||ExCellThera inc.|