US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04103879|
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : December 10, 2020
Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In a previous trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as >80% of patients received a 6-7/8 HLA matched CB. Interestingly there were patients with high-risk hematologic malignancies and multiple comorbidities (5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma). Despite this high risk population, progression was 20% at 12 months.
This new study seeks to test a similar strategy in a group of patients with high risk acute leukemia/myelodysplasia.
|Condition or disease||Intervention/treatment||Phase|
|High Risk Hematological Malignancy Cord Blood Transplant||Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Open-Label Study of UM171-Expanded Cord Blood Transplantation in Patients With High and Very High Risk Acute Leukemia/Myelodysplasia|
|Actual Study Start Date :||November 13, 2020|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2022|
Experimental: ECT-001-Expanded CB
Patients will receive a myeloablative conditioning regimen.
The cord to be expanded will undergo CD34+ selection. The CD34- product is cryopreserved and will be thawed and infused on Day +1 post-transplant. The CD34+ product will be placed in a closed culture with UM171 for a 7-day expansion and is infused on Day 0.
Patients will receive standard supportive care and GVHD prophylaxis (such as MMF and tacrolimus).
Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)
Conditioning: High dose TBI (1320 cGy TBI + Fludarabine 75 mg/m2 + Cyclophosphamide 120 mg/kg) or Intermediate Intensity regimen (400 cGy TBI + Fludarabine 150 mg/m2 + Cyclophosphamide 50 mg/kg + Thiotepa 10 mg/kg).
Single UM171-Expanded CB transplant (CD34+: 2.5-50x10E5/kg, CD3+>1x10E6/kg)
- Adverse events of ECT-001-CB [ Time Frame: 100 days ]All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)
- Adverse events of ECT-001-CB [ Time Frame: 2 years ]All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)
- Relapse-free survival [ Time Frame: At 1-year post-transplant ]RFS will be measured from time of transplant until disease relapse, death or last follow-up
- Relapse-free survival [ Time Frame: At 2-year post-transplant ]RFS will be measured from time of transplant until disease relapse, death or last follow-up
- Time to Neutrophil and Platelet engraftment [ Time Frame: First 60 days ]Neutrophil engraftment (the first day of attainment of an absolute neutrophil count ≥0.5 x 10E9/L for 3 consecutive days. Time to ANC ≥ 0.1 x 10E9/L will also be documented) and platelet engraftment (first day of a sustained platelet count ≥ 20 x 10E9/L with no platelet transfusion in the preceding 7 days)
- Incidence of transplant related mortality [ Time Frame: At day 100 and 1-year post-transplant ]TRM is defined as any death of any cause other than malignant relapse, occurring after the commencement of conditioning regimen that could be related to the transplantation procedure
- Incidence of GVHD [ Time Frame: At 2 years post-transplant ]Acute and chronic GVHD by NIH criteria
- Incidence of grade 3 or higher infectious complications [ Time Frame: At 2 years post-transplant ]Any of infections requiring systemic therapy, e.g., invasive candidiasis, aspergillus, other invasive fungi, CMV, adenovirus, EBV, HHV-6, HSV, VZV, PCP, toxoplasmosis and mycobacterium
- Incidence of pre-engraftment/engraftment syndrome requiring therapy [ Time Frame: At 2 years post-transplant ]
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): NCT04103879
|Contact: Filippo Milano, MD, PhD||(206) firstname.lastname@example.org|
|United States, Washington|
|Fred Hutchinson / University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Filippo Milano, MD, PhD 206-667-5925 email@example.com|