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Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05066165
Recruitment Status : Recruiting
First Posted : October 4, 2021
Last Update Posted : June 7, 2022
Sponsor:
Information provided by (Responsible Party):
Intellia Therapeutics

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : November 22, 2021
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : September 2025


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.





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

Secondary Outcome Measures :
  1. To characterize cell kinetics of NTLA-5001 via frequency of NTLA 5001 T cell receptor (TCR) transgene copy [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]
  2. To characterize cell kinetics of NTLA-5001 via persistence of NTLA 5001 T cell receptor (TCR) transgene copy [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]
  3. To estimate the antitumor activity of NTLA-5001 in participants with AML via tumor response [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]
  4. To estimate the antitumor activity of NTLA-5001 in participants with AML via response duration [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]
  5. To estimate the antitumor activity of NTLA-5001 in participants with AML via disease progression [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05066165


Contacts
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Contact: Trial Manager at Intellia 833-888-0387 clinicalscience@intelliatx.com

Locations
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United States, California
Research Site 2 Not yet recruiting
Los Angeles, California, United States, 90095
United States, Florida
Research Site 5 Recruiting
Tampa, Florida, United States, 33612
United States, Massachusetts
Research Site 1 Recruiting
Boston, Massachusetts, United States, 02114
United States, Oregon
Research Site 6 Recruiting
Portland, Oregon, United States, 97239
United States, Texas
Research Site 3 Recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
Research Site 4 Recruiting
Milwaukee, Wisconsin, United States, 53226
United Kingdom
Research Site 10 Not yet recruiting
Leeds, United Kingdom
Research Site 8 Recruiting
London, United Kingdom
Research Site 9 Not yet recruiting
London, United Kingdom
Research Site 7 Not yet recruiting
Manchester, United Kingdom
Sponsors and Collaborators
Intellia Therapeutics
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Responsible Party: Intellia Therapeutics
ClinicalTrials.gov Identifier: NCT05066165    
Other Study ID Numbers: ITL-5001-CL-001
First Posted: October 4, 2021    Key Record Dates
Last Update Posted: June 7, 2022
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Intellia Therapeutics:
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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms