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

Cord Blood Transplant Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04103879
• Other study ID #: ECT-001-CB.004
• Secondary ID: Study 8743
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 13, 2020
• Est. completion date: February 2026

Study information

• Verified date: February 2024
• Source: ExCellThera inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cord Blood Transplant
• Hematologic Neoplasms
• High Risk Hematological Malignancy
• Myelodysplastic Syndromes
• Preleukemia

Intervention

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

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam	GD
United States	University of Colorado School of Medicine. Anschutz Medical Campus	Aurora	Colorado
United States	Fred Hutchinson / University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
ExCellThera inc.	Fred Hutchinson Cancer Center

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events of ECT-001-CB	All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)	100 days post-transplant
Primary	Adverse events of ECT-001-CB	All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)	2 years post-transplant
Primary	Relapse-free survival	RFS will be measured from time of transplant until disease relapse, death or last follow-up	At 1-year post-transplant
Primary	Relapse-free survival	RFS will be measured from time of transplant until disease relapse, death or last follow-up	At 2-year post-transplant
Secondary	Time to Neutrophil and Platelet engraftment	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)	First 60 days
Secondary	Incidence of transplant related mortality	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	At day 100 post-transplant
Secondary	Incidence of transplant related mortality	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	At 1-year post-transplant
Secondary	Incidence of GVHD	Acute and chronic GVHD by NIH criteria	At 2 years post-transplant
Secondary	Incidence of grade 3 or higher infectious complications	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	At 2 years post-transplant
Secondary	Incidence of pre-engraftment/engraftment syndrome requiring therapy		At 2 years post-transplant
Secondary	GRFS and CRFS	GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up	At 1-year post-transplant
Secondary	GRFS and CRFS	GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up	At 2-year post-transplant