Sickle Cell DiseasePhase 1NCT04594031

US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease

A Phase 1 study testing ECT-001-CB (UM171-Expanded Cord Blood Transplant) in people with Sickle Cell Disease and Umbilical Cord Blood, run by ExCellThera inc. at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 5 to 30 years
Conditions the study is for: Sickle Cell Disease, Umbilical Cord Blood, Hematopoietic Cell Proliferation
What is being tested?: ECT-001-CB (UM171-Expanded Cord Blood Transplant)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 2 sitesUnited States
Study dates: 13 Jul 2021to 2 Feb 2024
Phase: Phase 1
Are there results?: None posted in the registry

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 5 to 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Be ≥ 5-30 years of age.
Have a diagnosis of SCD, with either βS/βS, βS/β0, βS/β+ or βS/βC genotype and followed at a center of excellence for SCD with at least 2 years of detailed past medical records available.
Have severe disease i.e. have experienced one or more of the following SCD related events, in spite of appropriate supportive care measures (e.g. pain management, penicillin prophylaxis):
Recurrent severe vaso-occlusive crisis (VOC) (≥2 episodes/year in the prior 2 years): an episode of pain lasting >2 hours severe enough to require care at a medical facility. Note that priapism that lasts >2 hours and requires care at a medical facility is also considered a VOC. To meet this criterion, subjects must have either experienced hydroxyurea failure at any point in the past (defined as >1 VOC or ≥1 acute chest syndrome (ACS) after taking hydroxyurea for ≥3 months) or must have intolerance to hydroxyurea (defined as inability to be maintained on an adequate dose of hydroxyurea due to marrow suppression or severe drug-induced toxicity [e.g. gastrointestinal distress, fatigue]).
ACS (≥2 total episodes in the prior 2 years, with at least one episode in the past year), defined as an acute event with pneumonia-like symptoms, hypoxemia and the presence of a new pulmonary infiltrate. To meet this criterion, subjects must have either experienced hydroxyurea failure or have intolerance to hydroxyurea, as defined above.
History of an overt stroke, defined as a sudden onset neurologic deficit lasting more than 24 hours that is accompanied by cerebral MRI changes.

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patients on chronic transfusions are eligible, provided medical records documenting any of the above severity criteria are available prior to starting the transfusion program.
Availability of 1 CB unit ≥ 6/8 HLA match (when A, B, C and DRB1 are performed at the allelic level resolution) with of at least CD34+ cell count 1.5 x 105/kg and total nucleated cells (TNC) 1.5 x 107/kg (pre-freeze)
Have adequate organ function to undergo a myeloablative (reduced toxicity conditioning) HSCT.
Have a Lansky/Karnofsky performance status of ≥ 80.
An appropriate and willing HLA-matched sibling donor is not available.

Who cannot join

Prior HSCT or gene-therapy.
Positive for presence of HIV-1 or HIV-2, hepatitis B virus (HBV), or hepatitis C virus (HCV). (Note that patients who have been vaccinated against hepatitis B [hepatitis B surface antibody (HBsAb)-positive] or patients with positive hepatitis B core and/or hepatitis B-e antibodies are also eligible provided viral load is negative by quantitative polymerase chain reaction (qPCR). Patients who are positive for anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load by qPCR). Positive serology for human T-lymphotropic virus-1 (HTLV-1), syphilis (rapid plasma reagin (RPR)), toxoplasmosis.
Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by PI.
A white blood cell count <2 × 10e9/L, and/or platelet count <50 × 10e9/L.
Any prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder.
Advanced liver disease, defined as:

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Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value >5 times the upper limit of normal (ULN); or
Cirrhosis or bridging fibrosis; or
Baseline prothrombin time or partial thromboplastin time > 1.5 x ULN; or
in chronically transfused patients a liver iron concentration (LIC) of ≥ 15 mg/g on T2* Magnetic Resonance Imaging [MRI] of liver.
Left ventricular ejection fraction (LVEF) <45% and for patients on chronic transfusions a cardiac T2* < 10 ms by MRI.
Baseline estimated glomerular filtration rate < 60 mL/min/1.73 m2.
Baseline oxygen saturation < 85% without supplemental oxygen (excluding periods of SCD crisis or infection).
Diffusion capacity of carbon monoxide (DLCO) <50% of predicted (corrected for hemoglobin and/or alveolar volume).
Any contraindication to general anaesthesia.
Participation in another clinical study with an investigational drug within 30 days of Screening.
Diagnosis of a significant psychiatric disorder as deemed as the PI that could seriously impede the subject's ability to participate in the study.
Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile patients. Females of child bearing potential are required to use effective contraception from enrollment through at least 6 months after drug product infusion. Male patients are required to use effective contraception from enrollment through at least 6 months after drug product infusion.
An assessment by the PI that the subject would not comply with the study procedures outlined in the protocol.
Any abnormal condition or laboratory result that is considered by the PI capable of altering patient condition or study outcome.
Note: should a patient be out of range for any numerical exclusion criteria, the PI is allowed to repeat the dosage once during the screening period to definitely determine eligibility

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Stanford University School of Medicine
Palo Alto, California, 94304
University of California San Francisco
San Francisco, California, 94158

Other trials in United States

About this study

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

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.

Conditions: Sickle Cell Disease, Umbilical Cord Blood, Hematopoietic Cell Proliferation
Being tested: ECT-001-CB (UM171-Expanded Cord Blood Transplant)
Medical subject headings: Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ECT-001-CB (UM171-Expanded Cord Blood Transplant)Biological
Single ECT-001-CB transplant (CD34+: 2 to 5.75x10E5/kg, CD3+ >1x10E6/kg)

Study groups in NCT04594031
Study group	Role	What they receive
ECT-001-CB	Experimental	* An Umbilical Cord Blood for transplant will undergo CD34+ selection and expansion. The CD34- fraction is infused on Day +1 post-transplant. * Patients will receive standard supportive care and GVHD prophylaxis Receives: Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)

What is being measured

The primary outcome is the main question the study is designed to answer.

Evaluate feasibility of finding a suitable ECT-001-CB graft for transplantation in the context of SCD.
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.
Measured: Up to 24-months
Evaluate feasibility of a successfully performing ECT-001-CB transplantation in the context of SCD.
Calculate the percentage of selected grafts that will be successfully expanded and transplanted with absence of technical hurdles
Measured: During accrual (up to 24-months)
Evaluate the Safety of ECT-001-CB by evaluating tri-lineage hematopoietic reconstitution
Measure the time required to achieve neutrophil and platelet engraftment
Measured: Up to 12-Months
Evaluate the Safety of ECT-001-CB by calculating incidence of acute and chronic GvHD
Calculate incidence of Acute GVHD and Chronic GVHD as per NIH criteria
Measured: Up to 12-Months
Evaluate the Safety of ECT-001-CB by evaluating adverse events
Calculate the Incidence of Adverse Events from the beginning of the conditioning regimen up to 12 months after ECT-001-CB transplant
Measured: Up to 12-Months
Evaluate the Safety of ECT-001-CB by evaluating incidence of transplant related mortality (TRM)
Calculate incidence of any mortality related to the investigational product until the end of evaluation period.
Measured: Up to 12-Months
Evaluate the Safety of ECT-001-CB by incidence of graft failure
Calculate the incidence of primary and late graft failure
Measured: Up to 100 days

Secondary outcomes (3)

Determine the pharmacologic effect of ECT-001-CB by evaluating donor chimerism
The percentage of hematopoietic chimerism, based on DNA polymorphisms, will be measured and compared to baseline.
Measured: Up to 12-Months post treatment
Determine the pharmacologic effect of ECT-001-CB by measuring sickle hemoglobin (HbS) in peripheral blood.
The concentration of the Sickle Hemoglobin (HbS) will be compared to baseline.
Measured: Up to 12-Months post treatment
Evaluate impact of ECT-001-CB on SCD-related events during the study period.
The incidence of SCD-related adverse events will be compared to internal controls
Measured: Up to 12-Months post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jul 20212 Feb 2024

First posted20 Oct 2020
Study start13 Jul 2021
Primary completion1 Sep 2023 (estimated)
Study completion2 Feb 2024 (estimated)

Why it stopped: Preference given to gene therapy approaches by the SCD research community and patients' associations

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
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
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04594031
Sponsor's protocol ID: ECT-001.CB.005
Status last verified: Jun 2022
First submitted: 28 Sep 2020
Last updated: 5 Jul 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04594031
Acronym / sponsor ID: ECT-001.CB.005
Conditions: Sickle Cell Disease, Umbilical Cord Blood, Hematopoietic Cell Proliferation
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Preference given to gene therapy approaches by the SCD research community and patients' associations
Enrolment: 0 participants (actual)
Lead sponsor: ExCellThera inc.Industry (pharma, biotech, devices)
Collaborators: California Institute for Regenerative Medicine (CIRM)
Study start: 13 Jul 2021 (actual)
Primary completion: 1 Sep 2023 (estimated)
Study completion: 2 Feb 2024 (estimated)
First posted: 20 Oct 2020 (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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ECT-001-CB	Experimental	Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)* An Umbilical Cord Blood for transplant will undergo CD34+ selection and expansion. The CD34- fraction is infused on Day +1 post-transplant. * Patients will receive standard supportive care and GVHD prophylaxis

Who may qualify

Ages: 5 to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (11 listed)

Be ≥ 5-30 years of age.
Have a diagnosis of SCD, with either βS/βS, βS/β0, βS/β+ or βS/βC genotype and followed at a center of excellence for SCD with at least 2 years of detailed past medical records available.
Have severe disease i.e. have experienced one or more of the following SCD related events, in spite of appropriate supportive care measures (e.g. pain management, penicillin prophylaxis):
Availability of 1 CB unit ≥ 6/8 HLA match (when A, B, C and DRB1 are performed at the allelic level resolution) with of at least CD34+ cell count 1.5 x 105/kg and total nucleated cells (TNC) 1.5 x 107/kg (pre-freeze)
Have adequate organ function to undergo a myeloablative (reduced toxicity conditioning) HSCT.

Key exclusion criteria (21 listed)

Prior HSCT or gene-therapy.
Positive for presence of HIV-1 or HIV-2, hepatitis B virus (HBV), or hepatitis C virus (HCV). (Note that patients who have been vaccinated against hepatitis B [hepatitis B surface antibody (HBsAb)-positive] or patients with positive hepatitis B core and/or hepatitis B-e antibodies are also eligible provided viral load is negative by quantitative polymerase chain reaction (qPCR). Patients who are positive for anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load by qPCR). Positive serology for human T-lymphotropic virus-1 (HTLV-1), syphilis (rapid plasma reagin (RPR)), toxoplasmosis.
Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by PI.
A white blood cell count <2 × 10e9/L, and/or platelet count <50 × 10e9/L.
Any prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder.

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
ECT-001-CB (UM171-Expanded Cord Blood Transplant)Single ECT-001-CB transplant (CD34+: 2 to 5.75x10E5/kg, CD3+ >1x10E6/kg)	Biological	ECT-001-CB

Primary outcome

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

3 secondary outcomes

Determine the pharmacologic effect of ECT-001-CB by evaluating donor chimerism
Time frame: Up to 12-Months post treatment
Determine the pharmacologic effect of ECT-001-CB by measuring sickle hemoglobin (HbS) in peripheral blood.
Time frame: Up to 12-Months post treatment
Evaluate impact of ECT-001-CB on SCD-related events during the study period.
Time frame: Up to 12-Months post treatment

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2022.
Individual participant dataSharing planned: No

Related trials for Sickle Cell Disease

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

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.

Medical Monitor study director

ExCellThera inc.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ECT-001-CB (UM171-Expanded Cord Blood Transplant) in people with Sickle Cell Disease and Umbilical Cord Blood, run by ExCellThera inc. at 2 sites 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 11 inclusion and 21 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: withdrawn, as of the sponsor's last update on 5 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Evaluate feasibility of finding a suitable ECT-001-CB graft for transplantation in the context of SCD. (time frame: Up to 24-months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04594031.

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 5 Jul 2022; AzTrials last refreshed its copy on 6 Nov 2026.