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Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Arm 1: NTLA-5001
Arm 2: NTLA-5001
Sponsored by
Intellia Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring NTLA-5001, cell kinetics, Pharmacodynamics, clustered regularly interspaced short palindromic repeats, CRISPR, AML, Acute Myeloid Leukemia, TCR T Cell Therapy, Autologous, Leukemia, Neoplasms, Immune System Diseases, Immunoproliferative Disorders

Eligibility Criteria

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

Inclusion Criteria (abbreviated):

  • Has AML as defined by World Health Organization
  • Has detectable disease following first-line therapy
  • Is ≥ 18 years of age.
  • Carries the human leukocyte antigen-A0201 (HLA-A*02:01) allele.
  • Has ECOG performance status of 0 to 1.
  • Has adequate absolute total lymphocyte count
  • Has adequate cardiac, renal, and liver organ function

Exclusion Criteria (abbreviated):

  • Has received AML-directed therapy or immunomodulatory therapy within a specified window prior to study entry.
  • Has received allogeneic hematopoietic cell transplant within 84 days, with ongoing GVHD, with recent DLI, or on active immunosuppression.
  • Has CNS involvement by tumor.
  • Has severe autoimmunity requiring immunomodulatory therapy.
  • Has active disseminated intravascular coagulation (DIC), bleeding or coagulopathy.
  • Has leukocytosis ≥ 20,000 blasts/μL despite hydroxyurea or has rapidly progressive disease
  • Has human immunodeficiency virus (HIV) infection, or any uncontrolled infection.
  • Female subjects are pregnant or breastfeeding; or are of childbearing potential and are unwilling to use protocol specified method of contraception.
  • Male subjects who have female partners of childbearing potential and are unwilling to use protocol specified method of contraception.

Sites / Locations

  • Research Site 2
  • Research Site 5
  • Research Site 1
  • Research Site 6
  • Research Site 3
  • Research Site 4
  • Research Site 10
  • Research Site 8
  • Research Site 9
  • Research Site 7

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: NTLA-5001

Arm 2: NTLA-5001

Arm Description

Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count <5%, administered by IV infusion following lymphodepleting chemotherapy.

Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count ≥5%, administered by IV infusion following lymphodepleting chemotherapy.

Outcomes

Primary Outcome Measures

Safety and tolerability as determined by adverse events (AEs) and dose-limiting toxicities (DLTs) (dose escalation only)

Secondary Outcome Measures

To characterize cell kinetics of NTLA-5001 via frequency of NTLA 5001 T cell receptor (TCR) transgene copy
To characterize cell kinetics of NTLA-5001 via persistence of NTLA 5001 T cell receptor (TCR) transgene copy
To estimate the antitumor activity of NTLA-5001 in participants with AML via tumor response
To estimate the antitumor activity of NTLA-5001 in participants with AML via response duration
To estimate the antitumor activity of NTLA-5001 in participants with AML via disease progression

Full Information

First Posted
September 23, 2021
Last Updated
February 7, 2023
Sponsor
Intellia Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05066165
Brief Title
Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
Official Title
Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Pivoting to an allogeneic version of this program currently in preclinical development.
Study Start Date
December 17, 2021 (Actual)
Primary Completion Date
July 21, 2022 (Actual)
Study Completion Date
August 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Intellia Therapeutics

4. Oversight

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

5. Study Description

Brief Summary
This study will be conducted to evaluate the safety, tolerability, cellular kinetics (CK), activity, and pharmacodynamics (PD) of NTLA-5001 in participants with Acute Myeloid Leukemia (AML).
Detailed Description
This 2-part first in human (FIH) study is comprised of two open-label arms. It is a multi-center, Phase 1/2a study evaluating the safety and activity of NTLA-5001 in subjects with persistent or recurrent Acute Myeloid Leukemia after first-line or later therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
NTLA-5001, cell kinetics, Pharmacodynamics, clustered regularly interspaced short palindromic repeats, CRISPR, AML, Acute Myeloid Leukemia, TCR T Cell Therapy, Autologous, Leukemia, Neoplasms, Immune System Diseases, Immunoproliferative Disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: NTLA-5001
Arm Type
Experimental
Arm Description
Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count <5%, administered by IV infusion following lymphodepleting chemotherapy.
Arm Title
Arm 2: NTLA-5001
Arm Type
Experimental
Arm Description
Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count ≥5%, administered by IV infusion following lymphodepleting chemotherapy.
Intervention Type
Genetic
Intervention Name(s)
Arm 1: NTLA-5001
Intervention Description
Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. Cyclophosphamide and Fludarabine will be administered on Day -5, -4, and -3 as intravenous infusion.
Intervention Type
Genetic
Intervention Name(s)
Arm 2: NTLA-5001
Intervention Description
Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. Cyclophosphamide and Fludarabine will be administered on Day -5, -4, and -3 as intravenous infusion.
Primary Outcome Measure Information:
Title
Safety and tolerability as determined by adverse events (AEs) and dose-limiting toxicities (DLTs) (dose escalation only)
Time Frame
From NTLA-5001 infusion up to week 112 post-infusion, primary DLT assessment up to 28 days post-infusion
Secondary Outcome Measure Information:
Title
To characterize cell kinetics of NTLA-5001 via frequency of NTLA 5001 T cell receptor (TCR) transgene copy
Time Frame
From NTLA-5001 infusion up to 112 weeks post-infusion
Title
To characterize cell kinetics of NTLA-5001 via persistence of NTLA 5001 T cell receptor (TCR) transgene copy
Time Frame
From NTLA-5001 infusion up to 112 weeks post-infusion
Title
To estimate the antitumor activity of NTLA-5001 in participants with AML via tumor response
Time Frame
From NTLA-5001 infusion up to 112 weeks post-infusion
Title
To estimate the antitumor activity of NTLA-5001 in participants with AML via response duration
Time Frame
From NTLA-5001 infusion up to 112 weeks post-infusion
Title
To estimate the antitumor activity of NTLA-5001 in participants with AML via disease progression
Time Frame
From NTLA-5001 infusion up to 112 weeks post-infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (abbreviated): Has AML as defined by World Health Organization Has detectable disease following first-line therapy Is ≥ 18 years of age. Carries the human leukocyte antigen-A0201 (HLA-A*02:01) allele. Has ECOG performance status of 0 to 1. Has adequate absolute total lymphocyte count Has adequate cardiac, renal, and liver organ function Exclusion Criteria (abbreviated): Has received AML-directed therapy or immunomodulatory therapy within a specified window prior to study entry. Has received allogeneic hematopoietic cell transplant within 84 days, with ongoing GVHD, with recent DLI, or on active immunosuppression. Has CNS involvement by tumor. Has severe autoimmunity requiring immunomodulatory therapy. Has active disseminated intravascular coagulation (DIC), bleeding or coagulopathy. Has leukocytosis ≥ 20,000 blasts/μL despite hydroxyurea or has rapidly progressive disease Has human immunodeficiency virus (HIV) infection, or any uncontrolled infection. Female subjects are pregnant or breastfeeding; or are of childbearing potential and are unwilling to use protocol specified method of contraception. Male subjects who have female partners of childbearing potential and are unwilling to use protocol specified method of contraception.
Facility Information:
Facility Name
Research Site 2
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site 5
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site 1
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site 6
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site 3
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site 4
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Research Site 10
City
Leeds
Country
United Kingdom
Facility Name
Research Site 8
City
London
Country
United Kingdom
Facility Name
Research Site 9
City
London
Country
United Kingdom
Facility Name
Research Site 7
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

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Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

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