Acute Myeloid LeukemiaPhase 1/2NCT05066165
Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
A Phase 1/2 study testing Arm 1: NTLA-5001 and Arm 2: NTLA-5001 in people with Acute Myeloid Leukemia, run by Intellia Therapeutics at 10 sites in 2 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Arm 1: NTLA-5001 and Arm 2: NTLA-5001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 17 Dec 2021to 31 Aug 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States6 sites
Research Site 1
Boston, Massachusetts, 02114
Research Site 3
Houston, Texas, 77030
Research Site 2
Los Angeles, California, 90095
Research Site 4
Milwaukee, Wisconsin, 53226
Research Site 6
Portland, Oregon, 97239
Research Site 5
Tampa, Florida, 33612
United Kingdom4 sites
Research Site 10
Leeds
Research Site 8
London
Research Site 9
London
Research Site 7
Manchester
About this study
Official title: Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
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).
Read the 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Arm 1: NTLA-5001, Arm 2: NTLA-5001
- 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
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Neoplasms, Immune System Diseases, Immunoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1: NTLA-5001Genetic
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-5001Genetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Genetic: Arm 2: NTLA-5001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Frequency of edited TCR transgene copy number in the peripheral blood of the participants was determined by droplet digital polymerase chain reaction (ddPCR).
Measured: From NTLA-5001 infusion up to 4 weeks post-infusion
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.
Measured: From NTLA-5001 infusion up to 4 weeks post-infusion
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).
Measured: From NTLA-5001 infusion up to 4 weeks post-infusion
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).
Measured: From NTLA-5001 infusion up to 4 weeks post-infusion
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
Measured: From NTLA-5001 infusion up to 4 weeks post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2021
- Study start17 Dec 2021
- Primary completion21 Jul 2022
- Study completion31 Aug 2022
Why it stopped: Pivoting to an allogeneic version of this program currently in preclinical development.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intellia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05066165
- Sponsor's protocol ID
- ITL-5001-CL-001
- Status last verified
- Dec 2023
- First submitted
- 23 Sep 2021
- Last updated
- 28 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05066165
- Acronym / sponsor ID
- ITL-5001-CL-001
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Pivoting to an allogeneic version of this program currently in preclinical development.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Intellia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 17 Dec 2021 (actual)
- Primary completion
- 21 Jul 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 4 Oct 2021 (actual)
- Results
- Posted 28 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: NTLA-5001 | Experimental | Genetic: Arm 1: NTLA-5001Up 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. |
| Arm 2: NTLA-5001 | Experimental | Genetic: Arm 2: NTLA-5001Up 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm 1: NTLA-5001Autologous 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. | Genetic | Arm 1: NTLA-5001 |
| Arm 2: NTLA-5001Autologous 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. | Genetic | Arm 2: NTLA-5001 |
Primary outcome
Participants That Experienced Dose-limiting Toxicities (DLTs)
Time frame: Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion
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.
5 secondary outcomes
Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood
Time frame: From NTLA-5001 infusion up to 4 weeks post-infusion
Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood
Time frame: From NTLA-5001 infusion up to 4 weeks post-infusion
Tumor Response in Participants With AML
Time frame: From NTLA-5001 infusion up to 4 weeks post-infusion
Response Duration in Participants With AML
Time frame: From NTLA-5001 infusion up to 4 weeks post-infusion
Disease Progression in Participants With AML
Time frame: From NTLA-5001 infusion up to 4 weeks post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Arm 1: NTLA-5001 and Arm 2: NTLA-5001 in people with Acute Myeloid Leukemia, run by Intellia Therapeutics at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants That Experienced Dose-limiting Toxicities (DLTs) (time frame: Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2023.