Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

NCT05066165 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ITL-5001-CL-001
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 10

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Participants That Experienced Dose-limiting Toxicities (DLTs)

  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 Outcomes (5)

• Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood

  From NTLA-5001 infusion up to 4 weeks post-infusion

• Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood

  From NTLA-5001 infusion up to 4 weeks post-infusion

• Tumor Response in Participants With AML

  From NTLA-5001 infusion up to 4 weeks post-infusion

• Response Duration in Participants With AML

  From NTLA-5001 infusion up to 4 weeks post-infusion

• Disease Progression in Participants With AML

  From NTLA-5001 infusion up to 4 weeks post-infusion

Study Arms (2)

Arm 1: NTLA-5001

EXPERIMENTAL

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

Arm 2: NTLA-5001

EXPERIMENTAL

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

Interventions

Arm 1: NTLA-5001 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 1: NTLA-5001

Arm 2: NTLA-5001 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Intellia Therapeutics: lead

Study Sites (10)

Research Site 2

Los Angeles, California, 90095, United States

Location

Research Site 5

Tampa, Florida, 33612, United States

Location

Research Site 1

Boston, Massachusetts, 02114, United States

Location

Research Site 6

Portland, Oregon, 97239, United States

Location

Research Site 3

Houston, Texas, 77030, United States

Location

Research Site 4

Milwaukee, Wisconsin, 53226, United States

Location

Research Site 10

Leeds, United Kingdom

Location

Research Site 8

London, United Kingdom

Location

Research Site 9

London, United Kingdom

Location

Research Site 7

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Neoplasms; Immune System Diseases; Immunoproliferative Disorders

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

The study was terminated by the Sponsor due to a strategic business decision.

Results Point of Contact

• Title: Trial Manager
• Organization: Intellia Therapeutics

clinicalscience@intelliatx.com

833-888-0387

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 4, 2021
• Study Start: December 17, 2021
• Primary Completion: July 21, 2022
• Study Completion: August 31, 2022
• Last Updated: December 28, 2023
• Results First Posted: December 28, 2023

Record last verified: 2023-12

Locations

US (6); GB (4)