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

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

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

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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

Resource links provided by the National Library of Medicine


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





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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

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): NCT04103879


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

Locations
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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

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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    Key Record Dates
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)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions