A Clinical Study of MK-4208/TERN-701 in Participants With Chronic Myeloid Leukemia (CML) (MK-4208-003/Tern701-1012/CARDINAL)

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

Trial locations and contacts

54 sites in 9 countries. Contact the study team or a site near you to ask about taking part.

About this study

Official title: A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Chronic Myeloid Leukemia, Chronic Phase, Chronic Myeloid Leukemia

Being tested

MK-4208

Keywords

allosteric inhibitor of BCR-ABL1, CML, TERN-701, chronic myeloid leukemia, T315I, T315I mutant, CARDINAL, HS-10382

Medical subject headings

Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase

What participants receive

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

• MK-4208Drug

  Also called Tern-701, HS-10382

  40 mg and 100 mg oral tablets

What is being measured

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

1. Part 1: Incidence of Dose Limiting Toxicities (DLTs) During the First Cycle of Intervention

   A DLT is any of a prespecified list of adverse events (AEs) of a pre-specified severity that occur during Cycle 1 (up to 28 days) if attributed to the study treatment and not attributed to any other clearly identifiable cause. The percentage of participants who experience DLTs will be reported. Each cycle is 28 days.

   Measured: Up to 28 days

2. Parts 1, 2m and 3: Number of Participants with at Least One AE

   An AE is any untoward medical occurrence in a participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding that is determined to be clinically significant by the investigator), symptom, or disease (new or exacerbated) temporally associated with the use of trial intervention. The number of participants with at least one AE will be reported.

   Measured: Up to 3 years

3. Parts 1, 2m and 3: Number of Participants with at Least One Serious Adverse Event (SAE)

   An SAE is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening; Requires in-patient hospitalization or prolongation of existing hospitalization; Results in persistent disability/incapacity; Is a congenital anomaly/birth defect; Other situations determined to be SAEs by the investigator. The number of participants with at least one SAE will be reported.

   Measured: Up to 3 years

4. Parts 1, 2m and 3: Number of Participants who Discontinued Study Intervention Due to an AE

   An AE is any untoward medical occurrence in a participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding that is determined to be clinically significant by the investigator), symptom, or disease (new or exacerbated) temporally associated with the use of trial intervention. The number of participants who discontinued study intervention due to an AE will be reported.

   Measured: Up to 3 years

5. Parts 2, 2m and 3: Number of Participants with a Complete Hematologic Response (CHR)

   The hematologic response will be evaluated by hematology and differential blood count. A CHR is defined by meeting all the following criteria and lasting for at least 4 weeks: Peripheral blood white blood cell count < 10 × 109/L ; Peripheral blood platelet count < 450 × 109/L; No immature cells in peripheral blood, such as myelocytes, promyelocytes, blasts and immature cells, and a basophil level < 5%; No symptoms or signs of the disease under trial, and the palpable splenomegaly has disappeared. The number of participants with a CHR will be reported.

   Measured: Baseline and up to 3 years

6. Parts 2, 2m and 3: Number of Participants with a Molecular response (MR)

   The MR will be evaluated for all participants, and peripheral blood will be collected and tested for breakpoint cluster region::Abelson (BCR::ABL1/ABLIS) using real-time quantitative polymerase chain reaction performed locally and centrally with validated polymerase chain reaction technology that has a sensitivity of at least 4.5 logs. An MR is defined as follows: MR1: BCR::ABL1IS > 1% to 10%; MR2: BCR::ABL1IS > 0.1% to 1%; MR3 (MMR): BCR::ABL1IS > 0.01% to 0.1%; MR4.0: BCR::ABL1IS > 0.0032% to 0.01%; MR4.5: BCR::ABL1IS > 0.001% to 0.0032%, MR5: ≤ 0.001%. The number of participants with a MR will be reported.

   Measured: Baseline and up to 3 years

7. Parts 2, 2m and 3: Number of Participants who had Best Categorical Shift in BCR-ABL1 Transcript Levels From Baseline

   The number of participants who had best categorical molecular response shift on treatment relative to baseline will be reported.

   Measured: Baseline and up to 3 years

Timeline

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

1. First posted8 Dec 2023
2. Study start26 Mar 2024
3. Primary completion30 Nov 2029 (estimated)
4. Study completion31 May 2030 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Other trials for Leukemia, Myelogenous, Chronic, BCR-ABL PositiveStudies 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.