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

Primary Purpose

High Risk Hematological Malignancy, Cord Blood Transplant

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ECT-001-CB (UM171-Expanded Cord Blood Transplant)

About this trial

This is an interventional treatment trial for High Risk Hematological Malignancy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
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
Karnofsky ≥70.
LVE fraction ≥ 40% or fractional shortening >22%
FVC, FEV1 and DLCOc ≥ 50% of predicted
Bilirubin < 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN.
Creatinine < 2.0 mg/dl.
HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old.

Exclusion Criteria:

Allogeneic myeloablative transplant within 6 months.
Autologous hematopoietic stem cell transplant within 6 months.
Active or recent invasive fungal infection.
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.
HIV positivity.
Hepatitis B or C infection with measurable viral load.
Liver cirrhosis.
Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome.
Active central nervous system involvement.
Chloroma > 2 cm.

Sites / Locations

University of Colorado School of Medicine. Anschutz Medical Campus
Fred Hutchinson / University of Washington Cancer Consortium
Erasmus Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ECT-001-Expanded CB

Arm Description

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).

Outcomes

Primary Outcome Measures

Adverse events of ECT-001-CB

All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)

Adverse events of ECT-001-CB

All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)

Relapse-free survival

RFS will be measured from time of transplant until disease relapse, death or last follow-up

Relapse-free survival

RFS will be measured from time of transplant until disease relapse, death or last follow-up

Secondary Outcome Measures

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)

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

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

Incidence of GVHD

Acute and chronic GVHD by NIH criteria

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

Incidence of pre-engraftment/engraftment syndrome requiring therapy

GRFS and CRFS

GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up

GRFS and CRFS

GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up

Full Information

NCT ID

NCT04103879

First Posted

September 23, 2019

Last Updated

September 5, 2023

Sponsor

ExCellThera inc.

Collaborators

Fred Hutchinson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT04103879

Brief Title

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 13, 2020 (Actual)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ExCellThera inc.

Collaborators

Fred Hutchinson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

High Risk Hematological Malignancy, Cord Blood Transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ECT-001-Expanded CB

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

ECT-001-CB (UM171-Expanded Cord Blood Transplant)

Intervention Description

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

Primary Outcome Measure Information:

Title

Adverse events of ECT-001-CB

Description

All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)

Time Frame

100 days post-transplant

Title

Adverse events of ECT-001-CB

Description

All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)

Time Frame

2 years post-transplant

Title

Relapse-free survival

Description

RFS will be measured from time of transplant until disease relapse, death or last follow-up

Time Frame

At 1-year post-transplant

Title

Relapse-free survival

Description

RFS will be measured from time of transplant until disease relapse, death or last follow-up

Time Frame

At 2-year post-transplant

Secondary Outcome Measure Information:

Title

Time to Neutrophil and Platelet engraftment

Description

Time Frame

First 60 days

Title

Incidence of transplant related mortality

Description

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

Time Frame

At day 100 post-transplant

Title

Incidence of transplant related mortality

Description

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

Time Frame

At 1-year post-transplant

Title

Incidence of GVHD

Description

Acute and chronic GVHD by NIH criteria

Time Frame

At 2 years post-transplant

Title

Incidence of grade 3 or higher infectious complications

Description

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

Time Frame

At 2 years post-transplant

Title

Incidence of pre-engraftment/engraftment syndrome requiring therapy

Time Frame

At 2 years post-transplant

Title

GRFS and CRFS

Description

GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up

Time Frame

At 1-year post-transplant

Title

GRFS and CRFS

Description

GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up

Time Frame

At 2-year post-transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: High and very high-risk hematologic malignancy defined as: Acute Myeloid Leukemia (Primary induction failure, Chemorefractory relapse, Relapse after allogeneic or autologous transplant, High risk AML in CR1, ≥ CR2) Acute Lymphoid leukemia (Primary induction failure, High risk ALL in CR1, ≥ CR2, Chemorefractory relapse, Relapse after allogeneic or autologous transplant) 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). Chronic myelogenous leukemia (Patients who progressed to blast crisis) 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 Karnofsky ≥70. LVE fraction ≥ 40% or fractional shortening >22% FVC, FEV1 and DLCOc ≥ 50% of predicted Bilirubin < 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN. Creatinine < 2.0 mg/dl. HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old. Exclusion Criteria: Allogeneic myeloablative transplant within 6 months. Autologous hematopoietic stem cell transplant within 6 months. Active or recent invasive fungal infection. 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. HIV positivity. Hepatitis B or C infection with measurable viral load. Liver cirrhosis. Pregnancy, breastfeeding or unwillingness to use appropriate contraception. Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome. Active central nervous system involvement. Chloroma > 2 cm.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Filippo Milano, MD, PhD

Phone

(206) 667-5925

fmilano@fredhutch.org

Facility Information:

Facility Name

University of Colorado School of Medicine. Anschutz Medical Campus

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Individual Site Status

Completed

Facility Name

Fred Hutchinson / University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Individual Site Status

Completed

Facility Name

Erasmus Medical Center

City

Rotterdam

State/Province

ZIP/Postal Code

3015

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jurjen Versluis, MD

Phone

+31 107040704

j.versluis.1@erasmusmc.nl

12. IPD Sharing Statement

Plan to Share IPD

Yes

Learn more about this trial

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

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