Clinical trial NCT04103879: US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: High Risk Hematological Malignancy
Cord Blood Transplant
Lead sponsor: ExCellThera inc.
Sponsor class: INDUSTRY
Collaborators: name: Fred Hutchinson Cancer Center
First posted: 2019-09-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. High and very high-risk hematologic malignancy defined as:

   1. Acute Myeloid Leukemia (Primary induction failure, Chemorefractory relapse, Relapse after allogeneic or autologous transplant, High risk AML in CR1, ≥ CR2)
   2. Acute Lymphoid leukemia (Primary induction failure, High risk ALL in CR1, ≥ CR2, Chemorefractory relapse, Relapse after allogeneic or autologous transplant)
   3. Myelodysplastic syndrome (Relapse after allogeneic or autologous transplant, ≥10% blasts within 30 days of start of conditioning regimen, Poor and very poor cytogenetics abnormalities, CMML with HCT-specific CPSS score high or intermediate-2, Stable disease, Progressive disease while on azacitidine).
   4. Chronic myelogenous leukemia (Patients who progressed to blast crisis)
2. Availability of 2 CBs ≥ 4/6 HLA match with pre-freeze CD34+ cell count ≥0.5 x 10E5/kg and TNC≥1.5 x 10E7/kg
3. Karnofsky ≥70.
4. LVE fraction ≥ 40% or fractional shortening \>22%
5. FVC, FEV1 and DLCOc ≥ 50% of predicted
6. Bilirubin \< 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN.
7. Creatinine \< 2.0 mg/dl.
8. HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old.

Exclusion Criteria:

1. Allogeneic myeloablative transplant within 6 months.
2. Autologous hematopoietic stem cell transplant within 6 months.
3. Active or recent invasive fungal infection.
4. Presence of a malignancy other than the one for which the UCB transplant is being performed and the expected survival related to the malignancy is estimated to be less than 75% at 5 years.
5. HIV positivity.
6. Hepatitis B or C infection with measurable viral load.
7. Liver cirrhosis.
8. Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
9. Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome.
10. Active central nervous system involvement.
11. Chloroma \> 2 cm.

Primary outcomes:
measure: Adverse events of ECT-001-CB
timeFrame: 100 days post-transplant
measure: Adverse events of ECT-001-CB
timeFrame: 2 years post-transplant
measure: Relapse-free survival
timeFrame: At 1-year post-transplant
measure: Relapse-free survival
timeFrame: At 2-year post-transplant
Secondary outcomes:
measure: Time to Neutrophil and Platelet engraftment
timeFrame: First 60 days
measure: Incidence of transplant related mortality
timeFrame: At day 100 post-transplant
measure: Incidence of transplant related mortality
timeFrame: At 1-year post-transplant
measure: Incidence of GVHD
timeFrame: At 2 years post-transplant
measure: Incidence of grade 3 or higher infectious complications
timeFrame: At 2 years post-transplant
measure: Incidence of pre-engraftment/engraftment syndrome requiring therapy
timeFrame: At 2 years post-transplant
measure: GRFS and CRFS
timeFrame: At 1-year post-transplant
measure: GRFS and CRFS
timeFrame: At 2-year post-transplant
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado School of Medicine. Anschutz Medical Campus
state: Colorado
city: Seattle
country: United States
facility: Fred Hutchinson / University of Washington Cancer Consortium
state: Washington
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: GD
Study officials:
References: