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A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)

Primary Purpose

Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
WU-NK-101
Sponsored by
Wugen, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring relapsed, refractory, leukemia, NK cells

Eligibility Criteria

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

Inclusion Criteria:

  1. Confirmed diagnosis of primary or secondary AML (any subtype except acute promyelocytic leukemia) according to World Health Organization (WHO) 2016 classification
  2. Unlikely to benefit from standard of care therapy defined by any one of the following criteria:

    1. Primary induction failure (PIF) defined as leukemia refractory to ≥ 1 induction attempts. Induction attempts include 1 high-dose and/or 2 standard-dose cytarabine

      • an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.
    2. For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens:

      • ≥ 2 but ≤ 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine
      • ≥ 2 but ≤ 4 cycles of gemtuzumab ozogamicin monotherapy
      • ≥ 6 but ≤ 8 cycles ivosidenib or enasidenib
    3. Leukemia in relapse after achieving CR

      • Early Relapse: disease recurrent within ≤ 6 month of documented remission
      • Late Relapse: disease recurrent within > 6 month of documented remission
      • Refractory-Relapse: refractory to ≥ 1 unsuccessful salvage attempts
  3. Patients with AML post hematopoietic stem cell transplant (HSCT) [permitted in Cohort Expansion Phase only] must meet the following criteria:

    • There must be histological confirmation of AML relapse after HSCT
    • Undergone allogeneic HSCT (alloSCT) > 90 days prior to enrollment from a match related donor, matched unrelated donor, cord blood donor, or haplo- identical donor
    • Off all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses (<10 mg) of corticosteroids
    • No history of Grade ≥ 3 veno-occlusive disease, or active graft versus host disease
  4. Patients with known central nervous system (CNS) involvement with AML are eligible if they have been treated and cerebrospinal fluid is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (radiotherapy or chemotherapy) should continue as medically indicated during the study treatment.
  5. Patients with extramedullary disease are permitted if bone marrow blast count is >5%
  6. Adequate organ function as defined in the protocol
  7. Life expectancy >12 weeks
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 at screening

Exclusion Criteria:

  1. Circulating blast count >30,000/µL by morphology or flow cytometry (cytoreductive therapies such as leukapheresis or hydroxyurea are allowed)
  2. Uncontrolled or untreated bacterial, fungal, or viral infections, including HIV, Hepatitis B or C infection, or uncontrolled infection of any etiology
  3. Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (ECG) suggestive of acute ischemia or active conduction system abnormalities
  4. Severe renal impairment, defined as creatinine clearance <40 mL/min
  5. 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).
  6. Known hypersensitivity to one or more of the study agents
  7. Received any investigational drugs within the 14 days prior to the first dose of fludarabine (wash-out period of at least 5 half-lives from the last dose of any investigational therapy prior to screening period or 14 days, whichever is longer)
  8. Pregnant or nursing (lactating) women
  9. Any condition that, in the opinion of the Investigator, would prevent the participant from consenting to or participating in the study

Sites / Locations

  • City of HopeRecruiting
  • Stanford Healthcare
  • Norton Health CareRecruiting
  • University of Maryland
  • Washington UniversityRecruiting
  • Providence Portland Medical CenterRecruiting
  • Peter MacCallum Cancer Center
  • Royal Perth Hospital
  • Royal Prince Alfred Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: WU-NK-101

Arm Description

A non-engineered Natural Killer (NK) cell derived from peripheral blood mononuclear cells (PBMC) that is cytokine-reprogrammed, expanded, and cryopreserved to create an allogeneic enhanced Memory-like anti-tumor NK cell therapy product. Each 28-day cycle of treatment consists of 3 doses of WU-NK-101 administered on Day 1, Day 8, and Day 15.

Outcomes

Primary Outcome Measures

Incidence of Adverse Events of WU-NK-101 as assessed by CTCAE v5
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until End of Study (EOS) visit.
Maximum Tolerated Dose
Maximum Tolerated or Administered Dose of WU-NK-101

Secondary Outcome Measures

Overall Survival
Time from study drug administration (Day 1) until death on study.
Duration of Response
Time of response to the time of disease relapse, progression, or death due to any cause.
Overall Response Rate (ORR)
ORR is defined as proportion of patients that achieve complete remission (CR) + complete remission with incomplete hematologic recover (CRi).

Full Information

First Posted
July 20, 2022
Last Updated
September 6, 2023
Sponsor
Wugen, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05470140
Brief Title
A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)
Official Title
A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2023 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wugen, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is a Phase 1, open-label, dose escalation, and cohort expansion study designed to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-leukemic activity of WU-NK-101 in R/R AML.
Detailed Description
This is a first in human, multi-center Phase 1 single agent study in patients with R/R AML who have exhausted other treatment options. The study will consist of two phases, dose escalation and cohort expansion. During the Dose Escalation Phase, up to 18 patients will be treated with WU-NK-101 in up to 3 Dose Levels (DL) until maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined. Once the MTD/MAD is defined, 6 additional patients will be enrolled in the Cohort Expansion Phase to further characterize the safety, tolerability, as well as determining the recommended phase 2 dose (RP2D) of WU-NK-101. Patients in the Cohort Expansion Phase, who achieve a partial response (PR), may receive up to 2 further re-induction cycles contingent on safety in the Dose Escalation Phase; patients who achieve a complete remission with partial hematologic recovery (CRh) or complete remission with incomplete hematologic recovery (CRi) at any point during the course of treatment may receive a further consolidation cycle, for a total of up to 4 cycles per patient. During cohort expansion, dosing breaks of up to two weeks are allowed between cycles.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
relapsed, refractory, leukemia, NK cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This study will determine the safety and tolerability of WU-NK-101 and define the RP2D.
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: WU-NK-101
Arm Type
Experimental
Arm Description
A non-engineered Natural Killer (NK) cell derived from peripheral blood mononuclear cells (PBMC) that is cytokine-reprogrammed, expanded, and cryopreserved to create an allogeneic enhanced Memory-like anti-tumor NK cell therapy product. Each 28-day cycle of treatment consists of 3 doses of WU-NK-101 administered on Day 1, Day 8, and Day 15.
Intervention Type
Biological
Intervention Name(s)
WU-NK-101
Intervention Description
WU-NK-101 administered on Day 1, Day 8, and Day 15.
Primary Outcome Measure Information:
Title
Incidence of Adverse Events of WU-NK-101 as assessed by CTCAE v5
Description
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until End of Study (EOS) visit.
Time Frame
24 months
Title
Maximum Tolerated Dose
Description
Maximum Tolerated or Administered Dose of WU-NK-101
Time Frame
Up to 21 days from first dose
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Time from study drug administration (Day 1) until death on study.
Time Frame
3 months
Title
Duration of Response
Description
Time of response to the time of disease relapse, progression, or death due to any cause.
Time Frame
24 months
Title
Overall Response Rate (ORR)
Description
ORR is defined as proportion of patients that achieve complete remission (CR) + complete remission with incomplete hematologic recover (CRi).
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Confirmed diagnosis of primary or secondary AML (any subtype except acute promyelocytic leukemia) according to World Health Organization (WHO) 2016 classification Unlikely to benefit from standard of care therapy defined by any one of the following criteria: Primary induction failure (PIF) defined as leukemia refractory to ≥ 1 induction attempts. Induction attempts include 1 high-dose and/or 2 standard-dose cytarabine an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens. For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens: ≥ 2 but ≤ 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine ≥ 2 but ≤ 4 cycles of gemtuzumab ozogamicin monotherapy ≥ 6 but ≤ 8 cycles ivosidenib or enasidenib Leukemia in relapse after achieving CR Early Relapse: disease recurrent within ≤ 6 month of documented remission Late Relapse: disease recurrent within > 6 month of documented remission Refractory-Relapse: refractory to ≥ 1 unsuccessful salvage attempts Patients with AML post hematopoietic stem cell transplant (HSCT) [permitted in Cohort Expansion Phase only] must meet the following criteria: There must be histological confirmation of AML relapse after HSCT Undergone allogeneic HSCT (alloSCT) > 90 days prior to enrollment from a match related donor, matched unrelated donor, cord blood donor, or haplo- identical donor Off all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses (<10 mg) of corticosteroids No history of Grade ≥ 3 veno-occlusive disease, or active graft versus host disease Patients with known central nervous system (CNS) involvement with AML are eligible if they have been treated and cerebrospinal fluid is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (radiotherapy or chemotherapy) should continue as medically indicated during the study treatment. Patients with extramedullary disease are permitted if bone marrow blast count is >5% Adequate organ function as defined in the protocol Life expectancy >12 weeks Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 at screening Exclusion Criteria: Circulating blast count >30,000/µL by morphology or flow cytometry (cytoreductive therapies such as leukapheresis or hydroxyurea are allowed) Uncontrolled or untreated bacterial, fungal, or viral infections, including HIV, Hepatitis B or C infection, or uncontrolled infection of any etiology Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (ECG) suggestive of acute ischemia or active conduction system abnormalities Severe renal impairment, defined as creatinine clearance <40 mL/min 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 (wash-out period of at least 5 half-lives from the last dose of any investigational therapy prior to screening period or 14 days, whichever is longer) Pregnant or nursing (lactating) women Any condition that, in the opinion of the Investigator, would prevent the participant from consenting to or participating in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eileen McNulty
Phone
314-501-1968
Email
info@wugen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan Davidson, MD, PhD
Organizational Affiliation
Wugen, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monz M Al Malki, MD
Facility Name
Stanford Healthcare
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lori Muffly, MD
Facility Name
Norton Health Care
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40299
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tabby Thomas
Email
tabby.thomas@nortonhealthcare.org
First Name & Middle Initial & Last Name & Degree
Don Stevens, MD
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sunita Phillips
Email
sphillip1@umm.edu
First Name & Middle Initial & Last Name & Degree
Ashkan Emadi, MD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katie Sticker
Email
kstricker@wustl.edu
First Name & Middle Initial & Last Name & Degree
Amanda Cashen, MD
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katrina Herz
Email
katrina.herz@providence.org
First Name & Middle Initial & Last Name & Degree
Natasha Edwin, MD
Facility Name
Peter MacCallum Cancer Center
City
Melbourne
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashish Bajel, MD
Email
enquiry@petermac.org
Facility Name
Royal Perth Hospital
City
Perth
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Megan Margaria
Email
megan.margaria@health.wa.gov.au
First Name & Middle Initial & Last Name & Degree
Peter Tan, MD
Facility Name
Royal Prince Alfred Hospital
City
Sydney
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose Valencia-Klug
Email
jose.valencia-klug@health.nsw.gob.au
First Name & Middle Initial & Last Name & Degree
Edward Abadir, MD

12. IPD Sharing Statement

Learn more about this trial

A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)

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