Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

Sponsor

Intellia Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT05066165

Collaborator

(none)

Enrollment

Locations

Arms

45.3

Anticipated Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

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

Study Type:

Interventional

Anticipated Enrollment :

54 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 :

Nov 22, 2021

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

Safety and tolerability as determined by adverse events (AEs) and dose-limiting toxicities (DLTs) (dose escalation only) [From NTLA-5001 infusion up to week 112 post-infusion, primary DLT assessment up to 28 days post-infusion]

Secondary Outcome Measures

To characterize cell kinetics of NTLA-5001 via frequency of NTLA 5001 T cell receptor (TCR) transgene copy [From NTLA-5001 infusion up to 112 weeks post-infusion]
To characterize cell kinetics of NTLA-5001 via persistence of NTLA 5001 T cell receptor (TCR) transgene copy [From NTLA-5001 infusion up to 112 weeks post-infusion]
To estimate the antitumor activity of NTLA-5001 in participants with AML via tumor response [From NTLA-5001 infusion up to 112 weeks post-infusion]
To estimate the antitumor activity of NTLA-5001 in participants with AML via response duration [From NTLA-5001 infusion up to 112 weeks post-infusion]
To estimate the antitumor activity of NTLA-5001 in participants with AML via disease progression [From NTLA-5001 infusion up to 112 weeks post-infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

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