A Study of Nemtabrutinib (MK-1026) (ARQ 531) in Participants With Selected Hematologic Malignancies

Sponsor
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03162536
Collaborator
(none)
190
Enrollment
10
Locations
10
Arms
74.2
Anticipated Duration (Months)
19
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to evaluate the safety, tolerability, pharmacodynamic, and pharmacokinetic (PK) of nemtabrutinib (formerly ARQ 531) tablets in selected participants with relapsed or refractory hematologic malignancies. No formal hypothesis testing will be performed for this study.

Detailed Description

This study includes 2 parts: Phase 1 (dose escalation) and Phase 2 (dose expansion). In Phase 1, participants will enroll using 3+3 dose escalation design. The starting dose of nemtabrutinib in oral tablet form was 5mg/day continuously. Dose escalation will continue until the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and dosing schedule is reached based on protocol-defined dose limiting toxicity (DLT). After the determination of the RP2D, 9 expansion cohorts will be initiated to evaluate the safety, tolerability, and efficacy of nemtabrutinib at RP2D in participants with specifically defined disease.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
190 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
Single group assignment (definition : A type of intervention model describing a clinical trial in which all participants receive the same intervention/treatment.)Single group assignment (definition : A type of intervention model describing a clinical trial in which all participants receive the same intervention/treatment.)
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of ARQ 531 in Selected Subjects With Relapsed or Refractory Hematologic Malignancies
Actual Study Start Date :
Jun 26, 2017
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Phase 1: Dose Escalation and Determination of RP2D

Phase I: Dose Escalation and determination of RP2D, multiple dose levels of nemtabrutinib to be evaluated (Up to approximately 22 months).

Drug: Nemtabrutinib
Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort A

    Relapsed/Refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) participants with at least 2 prior systemic therapies and previously treated with a covalent Bruton's tyrosine kinase inhibitor (BTKi) who must have a documented BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until progressive disease (PD), unacceptable adverse events (AEs), or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort B

    R/R CLL/SLL participants who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort C

    Richter's transformation (RT) participants who have failed at least one prior therapy receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort D

    Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort E

    Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort F

    Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort G

    High-grade B-cell lymphoma (BCL) participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations confirmed by flourescence in situ hybridization (FISH) or overexpression by immunohistochemistry (IHC) receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Cohort H

    Waldenström macroglobulinemia (WM) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Experimental: Phase 2: Expansion Food Effect Cohort I

    B-cell Non-Hodgkin's lymphoma (NHL), CLL/SLL and WM participants receive up to 65 mg of nemtabrutinib fasted (1 hour prior to or 2 hours after meal) and non-fasted per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 40 months).

    Drug: Nemtabrutinib
    Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.
    Other Names:
  • ARQ 531
  • MK-1026
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1: Number of Participants Experiencing Dose Limiting Toxicity (DLT) [Cycle 1 (up to 28 days)]

      DLT is defined by the occurrence of any of the following treatment emergent adverse event (TEAE) unless unequivocally due to the underlying malignancy or an extraneous cause within the first 28 days of study treatment (for dose escalation only) and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Any Grade 5 TEAE, any Grade 3 nonhematological TEAE except alopecia, nausea, vomiting, diarrhea, and transient Grade 3 laboratory abnormalities which recover within 1 week without intervention, any Grade 3 hematological TEAE that does not recover to Grade 1 or baseline within 7 days with the exception of Grade 3 lymphocytosis, which is considered to be an expected outcome of BTK inhibition, any Grade 4 nonhematological and hematological TEAE, or any other toxicity that in the view of the investigator represents a clinically significant hazard to the participant.

    2. Phase 1: Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 62 months]

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

    3. Phase 1: Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 61 months]

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

    4. Phase 2: Expansion Cohorts A, B & C: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by the Investigator [Up to approximately 24 weeks]

      ORR is defined as the percentage of participants achieving a best overall response of complete response (CR), partial response (PR) or partial response with lymphocytosis (PRL). iwCLL criteria as assessed by the investigator. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.

    5. Phase 2: Expansion Cohorts A, B, C: ORR per Lugano Classification as Assessed by the Investigator [Up to approximately 24 weeks]

      ORR is defined as percentage of participants achieving best overall response of CR/PR per Lugano classification as assessed by investigator. CR defined as EITHER CR by imaging (computed tomography [CT]): all lymph nodes normal (none ≥15 mm) & normal liver, spleen OR complete metabolic response (CMR): score of 1, 2 or3 on 5-point scale assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions (range: 1=no uptake above background to 5=uptake markedly higher than liver) AND bone marrow (BM) normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in sum of product of diameters [SPD] of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with score of 4/5 on FDG 5-point scale (with no new lesions) & decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.

    Secondary Outcome Measures

    1. Phase 2: Number of Participants Who Experienced an AE [Up to approximately 40 months]

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

    2. Phase 2: Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 39 months]

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

    3. Time to Maximum Concentration (Tmax) of Nemtabrutinib [Cycle 1: Days 1, 7 (Cohort I only), 8 (Cohort I only) & Cycle 2: Day 1: Predose and 1, 2, 4, 8, 24 hours postdose; Cycle 3: Day 1: Predose and 2 hours postdose (cycle length = 28 days)]

      Blood samples will be collected at prespecified time points to determine Tmax of nemtabrutinib.

    4. Maximum Concentration (Cmax) of Nemtabrutinib [Cycle 1: Days 1, 7 (Cohort I only), 8 (Cohort I only) & Cycle 2: Day 1: Predose and 1, 2, 4, 8, 24 hours postdose; Cycle 3: Day 1: Predose and 2 hours postdose (cycle length = 28 days)]

      Blood samples will be collected at prespecified time points to determine Cmax of nemtabrutinib.

    5. Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24hrs)of Nemtabrutinib [Cycle 1: Days 1, 7 (Cohort I only), 8 (Cohort I only) & Cycle 2: Day 1: Predose and 1, 2, 4, 8, 24 hours postdose; Cycle 3: Day 1: Predose and 2 hours postdose (cycle length = 28 days)]

      Blood samples will be collected at prespecified time points to determine AUC 0-24hrs of nemtabrutinib.

    6. Terminal Elimination Half-Life (t1/2) of Nemtabrutinib [Cycle 1: Days 1, 7 (Cohort I only), 8 (Cohort I only) & Cycle 2: Day 1: Predose and 1, 2, 4, 8, 24 hours postdose; Cycle 3: Day 1: Predose and 2 hours postdose (cycle length = 28 days)]

      t1/2 is the time it takes for the concentration of nemtabrutinib in the body to decrease by half during the elimination phase.

    7. Phase 2: Expansion Cohorts D-H: ORR per iwCLL Criteria as Assessed by the Investigator [Up to approximately 40 months]

      ORR is defined as the percentage of participants achieving a best overall response of complete response (CR), partial response (PR) or partial response with lymphocytosis (PRL). iwCLL criteria as assessed by the investigator. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.

    8. Phase 2: Expansion Cohorts D-H: ORR per Lugano classification as Assessed by the Investigator [Up to approximately 40 months]

      ORR is defined as percentage of participants achieving best overall response of CR/PR per Lugano classification as assessed by investigator. CR defined as EITHER CR by imaging (computed tomography [CT]): all lymph nodes normal (none ≥15 mm) & normal liver, spleen OR complete metabolic response (CMR): score of 1, 2 or3 on 5-point scale assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions (range: 1=no uptake above background to 5=uptake markedly higher than liver) AND bone marrow (BM) normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in sum of product of diameters [SPD] of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with score of 4/5 on FDG 5-point scale (with no new lesions) & decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.

    9. Phase 2: Expansion Cohorts A, B, H: Duration of Response (DOR) per iwCLL Criteria as Assessed by the Investigator [Up to approximately 40 months]

      DOR is defined as the time from the first documented evidence of CR or PR (or PRL for CLL/SLL participants) until progressive disease or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.

    10. Phase 2: Expansion Cohorts C-G: DOR per Laguna Classification As Assessed by Investiigator [Up to approximately 40 months]

      DOR is defined as time from first documented evidence of CR/PR (or PRL for CLL/SLL participants) until progressive disease or death due to any cause, whichever occurs first. CR defined as EITHER CR by imaging (computed tomography [CT]): all lymph nodes normal (none ≥15 mm) & normal liver, spleen OR complete metabolic response (CMR): score of 1, 2 or3 on 5-point scale assessing FDG metabolic activity in lymphomatous lesions (range: 1=no uptake above background to 5=uptake markedly higher than liver) AND BM normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR PMR with score of 4/5 on FDG 5-point scale (with no new lesions) & decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    Each prospective participant must meet ALL of the following inclusion criteria in order to be eligible for this study:

    • Signed written informed consent granted prior to initiation of any study-specific procedures

    • For the dose escalation cohorts, relapsed or refractory (R/R) participants with a diagnosis of B-cell Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and Waldenstrom macroglobulinemia (WM) who have received at least two prior systemic therapies . Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Participants with low grade lymphoma must be progressing and requiring treatment

    • For the expansion cohorts, the following criteria must be met:

    • Cohort A: R/R CLL/SLL participants with at least 2 prior systemic therapies and previously treated with a covalent Bruton's tyrosine kinase inhibitor (BTKi) who must have a documented Bruton's tyrosine kinase (BTK) mutation on C481 residue

    • Cohort B: R/R CLL/SLL participants who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue. In this study, intolerance to standard therapy is defined as having experienced a grade 3 or higher adverse event that was caused by the standard therapy and resulted in treatment discontinuation

    • Cohort C: Richter's transformation (RT) participants who have failed at least one prior therapy

    • Cohort D: Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A

    • Cohort E: Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies

    • Cohort F: Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies

    • Cohort G: High-grade B-cell lymphoma participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations

    • Cohort H: WM participants who have failed at least 2 prior systemic therapies

    • Disease status requirement:

    • For CLL participanst symptomatic disease that mandates treatment (Hallek et al.

    • For B-cell NHL participants, measurable disease by imaging scan

    • For WM, serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal (ULN)

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

    • Good organ function

    • Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation or by 24-hour urine collection

    • Total bilirubin ≤ 1.5 x institutional ULN (total bilirubin of ≤ 3 x institutional ULN in participants with documented Gilbert's syndrome)

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN

    • Platelet count ≥ 50,000/µL

    • Absolute neutrophil count (ANC) ≥ 1000/µL

    • Hemoglobin (Hgb) ≥ 8.0 g/dL, stable for ≥ 1 week.

    • For men and women of child-bearing potential, willing to use adequate contraception (e.g., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study

    • Female participants of child-bearing potential must have a negative serum pregnancy test within 14 days of the first day of drug dosing

    • Ability to swallow oral medications without difficulty

    Exclusion Criteria

    Potential participants who meet ANY of the following exclusion criteria are not eligible for enrollment into this study:

    • Had immunotherapy, radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 5 half-lives or four weeks (whichever is shorter) prior to treatment initiation, or oral therapy within 5 half-lives or one week (whichever is shorter) prior to treatment initiation

    • Transformation of follicular lymphoma (FL) to a more aggressive subtype of lymphoma or grade 3b FL

    • Participants currently being treated with the following drugs:

    • cytochrome P 450 (CYP) 2C9 substrates with a narrow therapeutic index (such as warfarin, phenytoin)

    • CYP 2C8 substrates with a narrow therapeutic index (such as paclitaxel)

    • CYP 2C19 substrates with a narrow therapeutic index (such as S-mephenytoin)

    • CYP 2D6 substrates with a narrow therapeutic index (such as thioridazine, pimozide)

    • P-gp substrates with a narrow therapeutic index (such as digoxin) Note: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment

    • Prior allogeneic bone marrow transplant

    • Active central nervous system (CNS) involvement

    • Pregnant or breast-feeding women

    • Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug

    • Uncontrolled illness including but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, cardiac infarction in the past six months, and psychiatric illness that would limit compliance with study requirements

    • QT corrected (QTc) prolongation (defined as a QTc > 450 msecs) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.

    • Active human immunodeficiency virus (HIV) infection, Hepatitis B, or Hepatitis C infection.

    • Other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the participant's safety or interfere with the evaluation of the safety of the study agent

    • History of prior cancer within < 1 year, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Mayo Clinic Hospital ( Site 0140)ScottsdaleArizonaUnited States85259
    2UCLA Hematology & Oncology ( Site 0017)Los AngelesCaliforniaUnited States90095
    3Colorado Blood Cancer Institute ( Site 0225)DenverColoradoUnited States80218
    4University of Michigan ( Site 0018)Ann ArborMichiganUnited States48109
    5Mayo Clinic - Rochester ( Site 0138)RochesterMinnesotaUnited States58905
    6Duke Cancer Center ( Site 0067)DurhamNorth CarolinaUnited States27710
    7The Ohio State University Wexner Medical Center ( Site 0056)ColumbusOhioUnited States43210
    8Tennessee Oncology, PLLC ( Site 0020)NashvilleTennesseeUnited States37203
    9UT Southwestern Medical Center ( Site 0116)DallasTexasUnited States75390-8562
    10University of Utah, Huntsman Cancer Institute ( Site 0122)Salt Lake CityUtahUnited States84112

    Sponsors and Collaborators

    • ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme Corp.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
    ClinicalTrials.gov Identifier:
    NCT03162536
    Other Study ID Numbers:
    • 1026-001
    • ARQ 531-101
    • MK-1026-001
    First Posted:
    May 22, 2017
    Last Update Posted:
    Mar 11, 2022
    Last Verified:
    Mar 1, 2022

    Study Results

    No Results Posted as of Mar 11, 2022