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Acute Myeloid LeukemiaPhase 1NCT05107856

PRT1419 as Monotherapy or in Combination With Azacitidine or Venetoclax in R/R Myeloid or B-cell Malignancies

A Phase 1 study testing PRT1419, Azacitidine and Venetoclax in people with Acute Myeloid Leukemia and B-cell Non-Hodgkin Lymphoma, run by Prelude Therapeutics Incorporated at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia-1 (MCL-1) inhibitor, in participants with selected relapsed/refractory myeloid or B-cell malignancies. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PRT1419, Azacitidine and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
9 sitesUnited States
Study dates
22 Mar 2022to 19 Jan 2024
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
  • Refractory/relapsed disease, having progressed on prior treatment, and without access to further approved therapies or ineligible for approved therapies, in one of the following disease categories: AML, CMML, MDS, MDS/MPN Overlap Syndrome, CLL/SLL, and B-cell NHLs
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 2
  • Adequate organ function (hematology, hepatic, renal, and coagulation)

Who cannot join

  • Active inflammatory disorders of the gastrointestinal tract, a history of bariatric surgery or other disorders with the potential for GI malabsorption
  • Cardiac function compromise, as assessed by echocardiogram or protocol-specified biochemical markers of cardiac damage, or protocol-defined clinically significant heart disease
  • History of cerebrovascular accident or transient ischemic attack, within 6 months of screening. Participants with a history of pulmonary embolism must not be symptomatic at enrollment
  • Undergone hematopoietic stem-cell transplantation (HSCT) within the last 90 days or have graft-versus-host disease (GVHD) Grade > 1 at study entry
  • Uncontrolled intercurrent illnesses, poorly controlled hypertension or dyslipidemias, Unstable central nervous system (CNS) metastases
  • Treatment with either OATP1B1, OATP1B3 substrates or strong inhibitors of CYP2C8, CYP3A4, and any medication contraindicated in combination with AZA or VEN
Show all 13Show fewer
  • Prior exposure to an MCL-1 inhibitor
  • Within 5 half-lives or 14 days (whichever is longer) following the last systemic anti-cancer therapy
  • History of another malignancy except for:
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated cervical or breast carcinoma in situ without evidence of disease
  • Asymptomatic prostate cancer without known metastatic disease and no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for >1 year prior to enrollment
  • Other malignancy treated with curative intent with no known active disease for > 2 years prior to enrollment

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • American Oncology Partners of Maryland, PA

    Bethesda, Maryland, 20817

  • New Jersey Center for Cancer Research

    Brick, New Jersey, 08724

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center - Main Campus

    New York, New York, 10065

  • Mid Florida Hematology and Oncology Center

    Orange City, Florida, 32763

  • AdventHealth Bone and Marrow Transplant Center

    Orlando, Florida, 32804

  • Thomas Jefferson University, Sidney Kimmel Cancer Center

    Philadelphia, Pennsylvania, 19107

  • North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists

    Port Jefferson Station, New York, 11776

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 Injection as Monotherapy or in Combination With Azacitidine or Venetoclax in Patients With Relapsed/Refractory Myeloid or B-cell Malignancies

This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia-1 (MCL-1) inhibitor, in participants with selected relapsed/refractory myeloid or B-cell malignancies. The purpose of this study is to evaluate the safety and tolerability of PRT1419 monotherapy and in combination with either azacitidine or venetoclax, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Read the detailed description

This is a multicenter, open-label, dose-escalation, Phase 1 study of PRT1419, a MCL-1 inhibitor, evaluating participants with acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasm (MPN) overlap syndrome, chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and B-cell non-hodgkin lymphoma (NHL) including marginal zone lymphoma, follicular lymphoma or mantle cell lymphoma. Participants in study will receive PRT1419 as monotherapy or in combination with either Azacitidine (AZA) or Venetoclax (VEN). The study includes multiple dose escalations and expansion cohorts for RP2D confirmation.

Being tested
PRT1419, Azacitidine, Venetoclax
Keywords
Acute Myeloid Leukemia (AML), Azacitidine, B-cell Malignancies, B-cell Non-Hodgkin lymphoma, Chronic lymphocytic leukemia (CLL), Chronic Myelomonocytic Leukemia (CMML), Follicular Lymphoma, Hematologic Malignancies, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Myelodysplastic Syndromes (MDS), Myeloid cell leukemia-1 (MCL-1), Myeloproliferative Neoplasm (MPN), PRT1419, Relapsed/Refractory Myeloid, Small lymphocytic lymphoma (SLL), Venetoclax
Medical subject headings
Leukemia, Myeloid, Acute, Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelomonocytic, Chronic, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PRT1419Drug

    PRT1419 will be administered by intravenous infusion

  • AzacitidineDrug

    Azacitidine will be administered by intravenous or subcutaneous

  • VenetoclaxDrug

    Venetoclax will be administered orally

Study groups in NCT05107856
Study groupRoleWhat they receive
PRT1419 MonotherapyExperimentalPRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned.
Receives: Drug: PRT1419
PRT1419/Azacitidine CombinationExperimentalPRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned and Azacitidine will be administered by intravenous or subcutaneous on Days 1 through 7 (or alternatively on Days 1 through 5, 8 and 9) of each 28-day treatment cycle.
Receives: Drug: PRT1419; Drug: Azacitidine
PRT1419/Venetoclax CombinationExperimentalPRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned and Venetoclax will be administered orally after either a 3-day or 5-week ramp-up period to reach 400 mg daily administration, prior to commencing PRT1419 administration.
Receives: Drug: PRT1419; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities (DLT) of PRT1419

    Dose limiting toxicities will be evaluated over the 28-day observation period

    Measured: Baseline through Day 28

  2. Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments

    Safety and tolerability will be assessed by recording adverse events (AEs), serious adverse events (SAEs), and DLTs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

    Measured: Baseline through approximately 3 years

  3. Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) and schedule of PRT1419

    The MTD/RP2D will be established for further investigation in participants with advanced hematologic malignancies

    Measured: Baseline through approximately 2 years

Secondary outcomes (8)

  1. Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: maximum observed plasma concentration

    PRT1419 pharmacokinetics will be calculated by maximum observed plasma concentration

    Measured: Baseline through approximately 3.5 years

  2. Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Time to maximal plasma concentration

    PRT1419 pharmacokinetics will be calculated by time to maximal plasma concentration (Tmax)

    Measured: Baseline through approximately 3.5 years

  3. Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Area under the curve

    PRT1419 pharmacokinetics will be calculated by area under the plasma concentration x time curve (AUC) from h 0 to the last measurable time point (AUC0-last)

    Measured: Baseline through approximately 3.5 years

  4. Safety and tolerability of PRT1419 in combination with AZA and VEN: AEs, SAEs, CTCAE assessments

    Safety and tolerability will be assessed by recording adverse events (AEs), serious adverse events (SAEs), and DLTs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

    Measured: Baseline through approximately 3 years

  5. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall response rate (ORR)

    Anti-tumor activity of PRT1419 based on the measurement of objective response rate (ORR) according to the disease-specific response criteria for malignancies under study

    Measured: Baseline through approximately 3.5 years

  6. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Progression-free survival (PFS)/event free survival (EFS)

    Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator according to the disease-specific response criteria for malignancies under study, or death due to any cause

    Measured: Baseline through approximately 3.5 years

  7. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Duration of response (DOR)

    Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator according to the disease-specific response criteria for malignancies under study, or death due to any cause

    Measured: Baseline through approximately 3.5 years

  8. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall survival (OS)

    Duration from Day 1 until death due to any cause

    Measured: Baseline through approximately 3.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2021
  2. Study start22 Mar 2022
  3. Primary completion19 Jan 2024
  4. Study completion19 Jan 2024

Why it stopped: Company Decision

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05107856
Sponsor's protocol ID
PRT1419-03
Status last verified
Jan 2024
First submitted
25 Oct 2021
Last updated
31 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PRT1419, Azacitidine and Venetoclax in people with Acute Myeloid Leukemia and B-cell Non-Hodgkin Lymphoma, run by Prelude Therapeutics Incorporated at 9 sites in United States.

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 4 inclusion and 13 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 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Company Decision). Results are not available in the source record.

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?

Dose limiting toxicities (DLT) of PRT1419 (time frame: Baseline through Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05107856.

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 31 Jan 2024.

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