Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05066165
• Other study ID #: ITL-5001-CL-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 17, 2021
• Est. completion date: August 31, 2022

Study information

• Verified date: December 2023
• Source: Intellia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: August 31, 2022
• Est. primary completion date: July 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.
• 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.

Locations

Country	Name	City	State
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 States	Research Site 1	Boston	Massachusetts
United States	Research Site 3	Houston	Texas
United States	Research Site 2	Los Angeles	California
United States	Research Site 4	Milwaukee	Wisconsin
United States	Research Site 6	Portland	Oregon
United States	Research Site 5	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Intellia Therapeutics

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood	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
Secondary	Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood	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
Secondary	Tumor Response in Participants With AML	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
Secondary	Response Duration in Participants With AML	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
Secondary	Disease Progression in Participants With AML	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