Clinical trial NCT05066165: Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
Official title: Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Intellia Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-10-04
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Participants That Experienced Dose-limiting Toxicities (DLTs)
timeFrame: Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion
Secondary outcomes:
measure: Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood
timeFrame: From NTLA-5001 infusion up to 4 weeks post-infusion
measure: Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood
timeFrame: From NTLA-5001 infusion up to 4 weeks post-infusion
measure: Tumor Response in Participants With AML
timeFrame: From NTLA-5001 infusion up to 4 weeks post-infusion
measure: Response Duration in Participants With AML
timeFrame: From NTLA-5001 infusion up to 4 weeks post-infusion
measure: Disease Progression in Participants With AML
timeFrame: From NTLA-5001 infusion up to 4 weeks post-infusion
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site 2
state: California
city: Tampa
country: United States
facility: Research Site 5
state: Florida
city: Boston
country: United States
facility: Research Site 1
state: Massachusetts
city: Portland
country: United States
facility: Research Site 6
state: Oregon
city: Houston
country: United States
facility: Research Site 3
state: Texas
city: Milwaukee
country: United States
facility: Research Site 4
state: Wisconsin
city: Leeds
country: United Kingdom
facility: Research Site 10
city: London
country: United Kingdom
facility: Research Site 8
city: London
country: United Kingdom
facility: Research Site 9
city: Manchester
country: United Kingdom
facility: Research Site 7
Study officials:
References: