Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03162536
Recruitment Status : Active, not recruiting
First Posted : May 22, 2017
Last Update Posted : March 11, 2022
Sponsor:
Information provided by (Responsible Party):
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

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.

Condition or disease Intervention/treatment Phase
Lymphoma, B-Cell Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia Waldenstrom Macroglobulinemia Mantle Cell Lymphoma Diffuse Large B Cell Lymphoma Richter's Transformation Follicular Lymphoma Marginal Zone Lymphoma Drug: Nemtabrutinib Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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.)
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 : June 26, 2017
Estimated Primary Completion Date : September 1, 2023
Estimated Study Completion Date : September 1, 2023


Arm Intervention/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




Primary Outcome Measures :
  1. Phase 1: Number of Participants Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. 2018)
    • 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

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): NCT03162536


Locations
Layout table for location information
United States, Arizona
Mayo Clinic Hospital ( Site 0140)
Scottsdale, Arizona, United States, 85259
United States, California
UCLA Hematology & Oncology ( Site 0017)
Los Angeles, California, United States, 90095
United States, Colorado
Colorado Blood Cancer Institute ( Site 0225)
Denver, Colorado, United States, 80218
United States, Michigan
University of Michigan ( Site 0018)
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic - Rochester ( Site 0138)
Rochester, Minnesota, United States, 58905
United States, North Carolina
Duke Cancer Center ( Site 0067)
Durham, North Carolina, United States, 27710
United States, Ohio
The Ohio State University Wexner Medical Center ( Site 0056)
Columbus, Ohio, United States, 43210
United States, Tennessee
Tennessee Oncology, PLLC ( Site 0020)
Nashville, Tennessee, United States, 37203
United States, Texas
UT Southwestern Medical Center ( Site 0116)
Dallas, Texas, United States, 75390-8562
United States, Utah
University of Utah, Huntsman Cancer Institute ( Site 0122)
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme LLC
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
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 ( Other Identifier: ArQule Protocol Number )
MK-1026-001 ( Other Identifier: Merck )
First Posted: May 22, 2017    Key Record Dates
Last Update Posted: March 11, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.):
nemtabrutinib
Hematologic Malignancies
SLL
CLL
B-cell NHL
WM
BTK (Brutons tyrosine kinase)
cancer
refractory
relapsed
Acalabrutinib
ArQule
BGB-3111
Blood Protein Disorders
Follicular Lymphoma
BTK Intolerant
C481
C481S
C481S Mutation
Cardiovascular Diseases
Chronic Lymphocytic Leukemia
DLBCL (Diffuse Large B-cell lymphoma)
GS-4059
Hemorrhagic Disorders
Hemostatic Disorders
Ibrutinib
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Leukemia, B-Cell
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Neoplasms
Lymphoma, Follicular
Leukemia, Lymphoid
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Neoplasms by Site
Hematologic Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders