Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

WU-NK-101 in Relapsed/Refractory AML and MDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04893915
Recruitment Status : Not yet recruiting
First Posted : May 20, 2021
Last Update Posted : June 18, 2021
Sponsor:
Collaborator:
Wugen, Inc.
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
This is a phase 2 study with a lead-in cohort of WU-NK-101, a cytokine-induced memory-like NK cell product derived from leukapheresed allogeneic donor NK cells activated ex vivo using HCW-9201, a GMP-grade fusion cytokine comprising IL-12, IL-15, and IL-18. Patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will receive lymphodepleting chemotherapy (Flu/Cy) and two infusions of WU-NK-101 at the previously defined maximum tolerated dose (MTD), fourteen days apart. Low dose rhIL-2 will be administered to patients for in vivo expansion following cell infusion. Patients will be assessed for anti-leukemic efficacy and safety. Re-infusion of patients who relapsed after clinical response will be considered.

Condition or disease Intervention/treatment Phase
Relapsed Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Myelodysplastic Syndromes Biological: WU-NK-01 Drug: Fludarabine Drug: Cyclophosphamide Procedure: Donor Leukapheresis Drug: Interleukin-2 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of WU-NK-101 in Relapsed/Refractory AML and MDS
Estimated Study Start Date : August 31, 2021
Estimated Primary Completion Date : February 28, 2024
Estimated Study Completion Date : February 28, 2024


Arm Intervention/treatment
Experimental: Lead In Cohort Recipient: WU-NK-101
  • Fludarabine and cyclophosphamide beginning on Day -6.
  • NK cell product will be infused on Day 0.
  • IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses.
  • NK cell product will be infused into the recipient on Day +14.
  • IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 26 for an additional 7 doses, and a total of 14 doses, to a maximum of two vials of rhIL-2 per IL-2 course.
  • In the Lead-in Cohort, three patients will receive WU-NK-101 on Day 0 and Day +14, receiving the maximum NK cells generated, capped at 20x10^6/kg.
  • Patients that have an initial response to WU-NK-101 but then subsequently relapse or progress will be able to receive a third dose of WU-NK-101 with or without lymphodepleting chemotherapy depending on the interval duration between the second dose and relapse, after approval by the study PI. The third dose should be administered not less than 45 days from Day 0.
Biological: WU-NK-01
Cell product processing is performed at the Siteman Cancer Center Biological Therapy Core or another FACT-accredited cellular therapy production facility that can manufacture WU-NK-101 per the IND CMC.

Drug: Fludarabine
-Lymphodepleting regimen

Drug: Cyclophosphamide
-Lymphodepleting regimen

Drug: Interleukin-2
-IL-2 will start approximately 2-4 hours after the WU-NK-101 infusions.
Other Name: IL-2

Experimental: Phase II Recipient: WU-NK-01
  • Fludarabine and cyclophosphamide beginning on Day -6.
  • NK cell product will be infused on Day 0.
  • IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses.
  • NK cell product will be infused into the recipient on Day +14.
  • IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 26 for an additional 7 doses, and a total of 14 doses, to a maximum of two vials of rhIL-2 per IL-2 course.
  • Will receive WU-NK-101 on Day 0 and Day +14, receiving the maximum NK cells generated, capped at 20x10^6/kg.
  • Patients that have an initial response to WU-NK-101 but then subsequently relapse or progress will be able to receive a third dose of WU-NK-101 with or without lymphodepleting chemotherapy depending on the interval duration between the second dose and relapse, after approval by the study PI. The third dose should be administered not less than 45 days from Day 0.
Biological: WU-NK-01
Cell product processing is performed at the Siteman Cancer Center Biological Therapy Core or another FACT-accredited cellular therapy production facility that can manufacture WU-NK-101 per the IND CMC.

Drug: Fludarabine
-Lymphodepleting regimen

Drug: Cyclophosphamide
-Lymphodepleting regimen

Drug: Interleukin-2
-IL-2 will start approximately 2-4 hours after the WU-NK-101 infusions.
Other Name: IL-2

Experimental: Donor
  • The allogeneic donor will undergo non-mobilized large volume (20-L) leukapheresis on Day -1.
  • On Day +13 the allogeneic donor will again undergo non-mobilized large volume (20-L) leukapheresis
Procedure: Donor Leukapheresis
-Apheresis will be performed via peripheral IVs or central line, as determined by the apheresis team.




Primary Outcome Measures :
  1. Overall response rate (ORR) of recipients [ Time Frame: Through 12 month follow-up ]
    • Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete blood count recovery (CRi).
    • Response will be assessed according to the criteria from the International Working Group Response Criteria


Secondary Outcome Measures :
  1. Overall survival (OS) of recipients [ Time Frame: Through completion of follow-up (estimated to be 12 months) ]
    -Defined as time from first dose of lymphodepleting chemotherapy (LDC) until death from any cause

  2. Event free survival (EFS) of recipients [ Time Frame: Through completion of follow-up (estimated to be 12 months) ]
    -Defined as time from first dose of lymphodepleting chemotherapy (LDC) until treatment failure, relapse from complete response, or death

  3. Duration of overall response (DOR) of recipients [ Time Frame: Through 12 month follow-up ]
    -Defined as duration for first occurrence of documented ORR until disease progression or death

  4. Duration of complete response (DoCR) of recipients [ Time Frame: Through 12 month follow-up ]
    -Defined as duration from documented complete remission until disease progression or death

  5. Proportion of recipients that receive multiple doses of WU-NK-101 [ Time Frame: Through Day +14 of all recipients enrolled (estimated to be 19 months) ]
  6. Number of dose-limiting toxicities (DLTs) that recipients experience in the safety lead-in cohort [ Time Frame: Through Day 28 ]
  7. Mortality rate of recipients [ Time Frame: Day +30 ]
  8. Mortality rate of recipients [ Time Frame: Day +100 ]
  9. Number of adverse events experienced by recipients [ Time Frame: Through Day +100 ]
    • Incidence, nature, and severity of adverse events
    • Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC < 500/µL) and adverse events of graft-versus-host disease (GVHD) involving the liver, skin, or gastrointestinal tract will be recorded until Day +100.

  10. Proportion of recipients with prolonged cytopenia [ Time Frame: At 8 weeks ]
  11. Change in quality of life experienced by recipients as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Day 0, Day +28, Day +100, 6 months, 9 months, and 12 months ]
  12. Overall response rate (ORR) of recipients compared across subgroups [ Time Frame: Through 12 month follow-up ]
    • Subgroups will be defined by degree of HLA-match from allogeneic donor
    • Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete blood count recovery (CRi).
    • Response will be assessed according to the criteria from the International Working Group Response Criteria

  13. Number of adverse events experienced by recipients compared across subgroups [ Time Frame: Through Day +100 ]
    • Subgroups will be defined by degree of HLA-match from allogeneic donor
    • Incidence, nature, and severity of adverse events
    • Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC < 500/µL) and adverse events of graft-versus-host disease (GVHD) involving the liver, skin, or gastrointestinal tract will be recorded until Day +100.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Refractory AML without CR after induction therapy (primary induction failure); relapsed AML after obtaining a CR; progressive AML after non-intensive therapy (e.g., HMA + venetoclax or targeted therapy); Intermediate risk to very-high-risk MDS by IPSS-R that is relapsed or refractory after prior therapy with an HMA-containing regimen
  • At least 18 years of age.
  • Available allogeneic donor that meets the following criteria:

    • Able and willing to undergo multiple rounds of leukapheresis
    • At least 18 years of age
    • In general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
    • Negative for hepatitis, HTLV, and HIV on donor viral screen
    • Not pregnant
    • Voluntary written consent to participate in this study
    • All HLA-match/mismatch statuses will be included, with preference for unmatched donors all else being equal
  • Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
  • Karnofsky/Lansky performance status > 50 %
  • Adequate organ function as defined below:

    • Total bilirubin < 2 mg/dL
    • AST(SGOT)/ALT(SGPT) < 3.0 x ULN
    • Creatinine within normal institutional limits OR creatinine clearance ≥ 40 mL/min by Cockcroft-Gault Formula
    • Oxygen saturation ≥90% on room air
    • Ejection fraction ≥35%
  • Able to be off corticosteroids and any other immune suppressive medications beginning on Day -3 and continuing until 30 days after the last infusion of the WU-NK-101. However, use of low-level corticosteroids is permitted if deemed medically necessary. Low-level corticosteroid use is defined as 10mg or less of prednisone (or equivalent for other steroids) per day.
  • Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and until 30 days after the last WU-NK-101 infusion.
  • Ability to understand and willingness to sign an IRB approved written informed consent document

Exclusion Criteria:

  • Relapsed after allogeneic transplantation.
  • Circulating blast count >30,000/µL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed).
  • Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
  • Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
  • New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections).
  • Known hypersensitivity to one or more of the study agents.
  • Received any investigational drugs within the 14 days prior to the first dose of fludarabine.
  • Pregnant and/or breastfeeding.
  • Any condition that, in the opinion of the investigator, would prevent the participant from consenting to or participating in the study

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): NCT04893915


Contacts
Layout table for location contacts
Contact: Amanda Cashen, M.D. 314-434-8323 acashen@wustl.edu

Locations
Layout table for location information
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Contact: Amanda Cashen, M.D.    314-434-8323    acashen@wustl.edu   
Principal Investigator: Amanda Cashen, M.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: John DiPersio, M.D., Ph.D.         
Sub-Investigator: Meagan Jacoby, M.D., Ph.D.         
Sub-Investigator: Iskra Pusic, M.D.         
Sub-Investigator: Mark Schroeder, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Matthew Walter, M.D.         
Sub-Investigator: Lukas Wartman, M.D.         
Sub-Investigator: John Welch, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: Brad Kahl, M.D.         
Sub-Investigator: Scott Goldsmith, M.D.         
Sub-Investigator: Ramzi Abboud, M.D.         
Sub-Investigator: Fei Wan, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Wugen, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Amanda Cashen, M.D. Washington University School of Medicine
Additional Information:
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04893915    
Other Study ID Numbers: 202106075
First Posted: May 20, 2021    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Cyclophosphamide
Fludarabine
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents