Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

December 14, 2023 updated by: Intellia Therapeutics

Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Leeds, United Kingdom
        • Research Site 10
      • London, United Kingdom
        • Research Site 8
      • London, United Kingdom
        • Research Site 9
      • Manchester, United Kingdom
        • Research Site 7
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Research Site 2
    • Florida
      • Tampa, Florida, United States, 33612
        • Research Site 5
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Research Site 1
    • Oregon
      • Portland, Oregon, United States, 97239
        • Research Site 6
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site 3
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Research Site 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
From NTLA-5001 infusion up to 4 weeks post-infusion
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.
From NTLA-5001 infusion up to 4 weeks post-infusion
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).
From NTLA-5001 infusion up to 4 weeks post-infusion
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).
From NTLA-5001 infusion up to 4 weeks post-infusion
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
From NTLA-5001 infusion up to 4 weeks post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intellia Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 17, 2021

Primary Completion (Actual)

July 21, 2022

Study Completion (Actual)

August 31, 2022

Study Registration Dates

First Submitted

September 23, 2021

First Submitted That Met QC Criteria

September 23, 2021

First Posted (Actual)

October 4, 2021

Study Record Updates

Last Update Posted (Actual)

December 28, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ITL-5001-CL-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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