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Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT05066165
Recruitment Status : Terminated (Pivoting to an allogeneic version of this program currently in preclinical development.)
First Posted : October 4, 2021
Results First Posted : December 28, 2023
Last Update Posted : December 28, 2023
Sponsor:
Information provided by (Responsible Party):
Intellia Therapeutics

Study Description
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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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Genetic: Arm 1: NTLA-5001 Genetic: Arm 2: NTLA-5001 Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
Actual Study Start Date : December 17, 2021
Actual Primary Completion Date : July 21, 2022
Actual Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1: NTLA-5001
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.
 Genetic: Arm 1: NTLA-5001

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.
Experimental: Arm 2: NTLA-5001
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.
 Genetic: Arm 2: NTLA-5001

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.


Outcome Measures
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Primary Outcome Measures :
  1. Participants That Experienced Dose-limiting Toxicities (DLTs) [ Time Frame: Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion ]
    DLTs were defined as events with onset within 28 days of infusion. AEs were collected from time of informed consent through the Week 112 visit. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. Severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 toxicity grading criteria. The measure reported below for the primary outcome consists of DLT data only. Adverse events are reported in the Adverse Event section of this presentation.


Secondary Outcome Measures :
  1. Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
    Frequency of edited TCR transgene copy number in the peripheral blood of the participants was determined by droplet digital polymerase chain reaction (ddPCR).

  2. Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
    Persistence of edited TCR transgene copy in the peripheral blood of the participants determined by ddPCR.

  3. Tumor Response in Participants With AML [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
    Rate of objective response, where response is complete response without measurable residual disease (CRMRD-) (Arm 1). Rate of objective response, where response is CRMRD-, complete response, complete remission with incomplete hematologic recovery, morphologic leukemia-free state, and partial remission (Arm 2).

  4. Response Duration in Participants With AML [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
    Bone marrow results were planned to be used to determine the duration of response / remission (DOR) for subjects with objective response, from first response until MRD was measured above the lower level of detection for the central laboratory assay, or death from any cause, whichever occurred first (Arm 1). Bone marrow results were planned to be used to determine DOR for subjects with composite CR, from first response to progression or death due to any cause, whichever occurred first (Arm 2).

  5. Disease Progression in Participants With AML [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
    Bone marrow results were used to determine the time to clinical progression. Progressive disease was defined as an increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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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): NCT05066165


Locations
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United States, California
Research Site 2
Los Angeles, California, United States, 90095
United States, Florida
Research Site 5
Tampa, Florida, United States, 33612
United States, Massachusetts
Research Site 1
Boston, Massachusetts, United States, 02114
United States, Oregon
Research Site 6
Portland, Oregon, United States, 97239
United States, Texas
Research Site 3
Houston, Texas, United States, 77030
United States, Wisconsin
Research Site 4
Milwaukee, Wisconsin, United States, 53226
United Kingdom
Research Site 10
Leeds, United Kingdom
Research Site 8
London, United Kingdom
Research Site 9
London, United Kingdom
Research Site 7
Manchester, United Kingdom
Sponsors and Collaborators
Intellia Therapeutics
  Study Documents (Full-Text)

Documents provided by Intellia Therapeutics:
Study Protocol  [PDF] December 22, 2021
Statistical Analysis Plan  [PDF] January 6, 2023

More Information
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Responsible Party: Intellia Therapeutics
ClinicalTrials.gov Identifier: NCT05066165    
Other Study ID Numbers: ITL-5001-CL-001
First Posted: October 4, 2021    Key Record Dates
Results First Posted: December 28, 2023
Last Update Posted: December 28, 2023
Last Verified: December 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Intellia Therapeutics:
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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
 Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases