UM171 Expanded Cord Blood In Patients With High-Risk Acute Leukemia/Myelodysplasia
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|ClinicalTrials.gov Identifier: NCT03913026|
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : January 27, 2020
Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients with blood cancers. Cord blood (CB) represents an alternative source of stem cells, which is associated with a lower risk of relapse, especially in the presence of minimal residual disease in the setting of acute leukemia and myelodysplasia. Furthermore, CB has the added advantage of being associated with a low risk of chronic graft versus host disease (GVHD). Unfortunately, CB transplants are hampered by a higher risk of transplant related mortality (TRM) when compared to bone marrow/peripheral blood transplants because of the limited cell dose of CB.
In the previous UM171 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 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. Hence, in this new trial, investigators are targeting patients with high and very high-risk acute leukemia/myelodysplasia to test the antileukemia effect of this new graft, a UM171 expanded CB.
|Condition or disease||Intervention/treatment||Phase|
|High Risk Hematologic Malignancy Cord Blood Transplant||Biological: Transplant with an expanded ECT-001 cord blood||Phase 2|
This is a multi-center open label phase II clinical trial. Patients with high and very high-risk acute leukemia/myelodysplasia will receive a single 5-7/8 HLA matched ECT-001 (UM171) expanded cord blood after an ablative conditioning regimen. This group of patients would be expected to have poor progression free survival (PFS) after a conventional allogeneic transplant (bone marrow-peripheral blood).
Investigators key primary and secondary objectives include:
- To confirm low Transplant Related Mortality (TRM)
- To evaluate relapse free survival (RFS)
- To analyze kinetics of hematologic engraftment;
- To evaluate the incidence of acute and chronic GVHD
- To evaluate the safety of the procedure
- To evaluate incidence of infectious complications
- To analyze duration of hospitalization
- To evaluate the incidence of pre-engraftment/engraftment syndrome (PES/ES)
- To analyze the effect of cryopreservation of the expanded CD34+ fraction on safety and efficacy endpoints
|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 ECT-001-expanded Cord Blood Transplantation in Patients With High-risk Acute Leukemia/Myelodysplasia|
|Actual Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
Experimental: Main intervention
Eligible patients will receive an ablative conditioning regimen and be infused with an ECT-001 expanded cord-blood. The ECT-001 expanded CB could be infused fresh, or cryopreserved.
Biological: Transplant with an expanded ECT-001 cord blood
- Transplant Related Mortality (TRM) [ Time Frame: 1 year ]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.
- Relapse Free survival (RFS) [ Time Frame: 2 years ]RFS will be measured from time of transplant until disease relapse, death or last follow-up.
- Overall survival (OS) [ Time Frame: 2 years ]OS will be measured from time of transplant until disease relapse, death or last follow-up.
- Neutrophil Engraftment [ Time Frame: 42 days ]Time to neutrophil engraftment is defined as the first day of attainment of an absolute neutrophil count (ANC) ≥0.5 x 109/L for 3 consecutive days. Time to ANC ≥ 0.1 x 109/L will also be documented as it seems to predict TRM.
- Graft failure [ Time Frame: 42 days ]Absence of neutrophil engraftment by day 42 or secondary graft failure without any obvious cause.
- Platelet Engraftment [ Time Frame: 60 days ]Platelet engraftment is defined as the first day of a sustained platelet count ≥ 20 x 109/L with no platelet transfusion in the preceding 7 days as per CIBMTR standards (www.cibmtr.org).
- Incidence of Acute Graft Versus Host Disease (aGVHD) [ Time Frame: 1 year ]The time to onset and maximal grade will be recorded. Acute GVHD will be defined as classic acute (time of onset of symptoms ≤ 100 days) or persistent, recurrent, or late onset acute GVHD (time of onset of symptoms > 100 days) as defined by the NIH. Results will be compared to patients at the same institution transplanted with different stem cell sources.
- Incidence of Chronic Graft Versus Host Disease (cGVHD) [ Time Frame: 2 years ]Defined as per NIH global severity scores for mild, moderate, and severe chronic GVHD.
- Adverse events grade 3 or higher [ Time Frame: 3 years ]All adverse events occurring during the clinical trial, including the protocol-defined post-treatment follow-up period, qualifying as a grade ≥ 3 toxicity per the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Incidence of severe infectious complications. [ Time Frame: 3 years ]Any of the following infections requiring systemic therapy will be captured: invasive candidiasis, aspergillus, other invasive fungi, CMV, adenovirus, EBV, HHV-6, HSV, VZV, PCP, toxoplasmosis and mycobacterium.
- Hospitalization events [ Time Frame: 1 year ]Total number of days admitted to the hospital in the first 100 days following transplant. Last day of fever (≥38.0°C) prior to engraftment, and number of days of parenteral feeding during transplant admission.
- Incidence of preengraftment/engraftment syndrome (ES) requiring therapy. [ Time Frame: 30 days ]
- Immune reconstitution [ Time Frame: 1 year ]T, B, NK cell evaluation
- Identify markers suggesting escape from the immune system [ Time Frame: 3 years ]If the underlying disease recurs, sequencing will be performed of the leukemias/MDS to identify markers suggesting escape from the immune system: for example down regulation of HLA on cancer cells.
- Graft composition and evaluation [ Time Frame: 7 days ]To better understand the effect of ECT-001 expansion a sample of the graft will be transplanted into mice before and after expansion. In addition, the different cell populations of the graft will be analyzed by flow cytometry before and after expansion. UM171 appears to increase significantly the proportion of dendritic cell precursors and mast cell precursors. Confirmation of this observation from the 1st trial will be obtained.
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): NCT03913026
|Contact: Sandra Cohen, MDfirstname.lastname@example.org|
|CIUSSS de l'Est-de-l'île-de Montreal, Hôpital Maisonneuve-Rosemont||Recruiting|
|Montréal, Quebec, Canada, H1T2M4|
|Contact: Hocine Ait Hamouda, MSc 5142523400 ext 3609 email@example.com|
|Principal Investigator: Sandra Cohen, MD|
|Principal Investigator:||Sandra Cohen, MD||Ciusss de L'Est de l'Île de Montréal|