Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

NCT ID: NCT05066165

Last Updated: 2023-12-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-17

Study Completion Date

2022-08-31

Brief Summary

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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

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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.

Conditions

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Acute Myeloid Leukemia

Keywords

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Arm 1: NTLA-5001

Intervention Type GENETIC

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.

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.

Group Type EXPERIMENTAL

Arm 2: NTLA-5001

Intervention Type GENETIC

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.

Interventions

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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.

Intervention Type 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.

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Intellia Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site 2

Los Angeles, California, United States

Site Status

Research Site 5

Tampa, Florida, United States

Site Status

Research Site 1

Boston, Massachusetts, United States

Site Status

Research Site 6

Portland, Oregon, United States

Site Status

Research Site 3

Houston, Texas, United States

Site Status

Research Site 4

Milwaukee, Wisconsin, United States

Site Status

Research Site 10

Leeds, , United Kingdom

Site Status

Research Site 8

London, , United Kingdom

Site Status

Research Site 9

London, , United Kingdom

Site Status

Research Site 7

Manchester, , United Kingdom

Site Status

Countries

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United States United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ITL-5001-CL-001

Identifier Type: -

Identifier Source: org_study_id