US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia

• ClinicalTrials.gov Identifier: NCT04103879
• Recruitment Status: Recruiting
• First Posted: September 26, 2019
• Last Update Posted: September 27, 2019
• Sponsor: ExCellThera inc.
• Collaborator: Fred Hutchinson Cancer Research Center
• Information provided by (Responsible Party): ExCellThera inc.

Study Description

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.

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: September 2019
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm

Intervention/treatment

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) Immunosuppression: Tacrolimus/MMF

Outcome Measures

Primary Outcome Measures :

1. 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)
2. 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)
3. 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
4. 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

Secondary Outcome Measures :

1. 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)
2. 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
3. Incidence of GVHD [ Time Frame: At 2 years post-transplant ]
   Acute and chronic GVHD by NIH criteria
4. 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
5. Incidence of pre-engraftment/engraftment syndrome requiring therapy [ Time Frame: At 2 years post-transplant ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Filippo Milano, MD, PhD; (206) 667-5925; fmilano@fredhutch.org

Locations

United States, Washington

Fred Hutchinson / University of Washington Cancer Consortium; Recruiting

Seattle, Washington, United States, 98109

Contact: Filippo Milano, MD, PhD 206-667-5925 fmilano@fredhutch.org

Sponsors and Collaborators

ExCellThera inc.

Fred Hutchinson Cancer Research Center

More Information

• Responsible Party: ExCellThera inc.
• ClinicalTrials.gov Identifier: NCT04103879 History of Changes
• Other Study ID Numbers: ECT-001-CB.004; Study 8743 ( Other Identifier: FHCRC )
• First Posted: September 26, 2019
• Last Update Posted: September 27, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Clinical Study Report (CSR)

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Preleukemia; Myelodysplastic Syndromes; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions