Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ARQ 531
Previous Study | Return to List | Next Study

A Study of ARQ 531 in Patients 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03162536
Recruitment Status : Recruiting
First Posted : May 22, 2017
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
ArQule

Brief Summary:
This is an open-label, multi-center Phase 1/2 study of ARQ 531 in patients with selected hematologic malignancies.

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: ARQ 531 Phase 1 Phase 2

Detailed Description:
This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, patients were enrolled using 3+3 dose escalation design. The starting dose of ARQ 531 in oral tablet form was 5mg/day continuously. The RP2D has been determined at 65mg/day, patients will be enrolled to one of 8 cohorts depending on tumor histology and prior treatment history. Cycle length will be 28 days.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 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 : July 10, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: Phase I : Dose Escalation and Determination of RP2D
Phase I : Dose Escalation and determination of RP2D, multiple dose levels of ARQ 531 to be evaluated
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : Relapsed/Refractory (R/R) CLL/SLL subjects
Phase II : Relapsed/Refractory (R/R) CLL/SLL subjects 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
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : R/R CLL/SLL Subjects
Phase II : R/R CLL/SLL subjects who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : Richter's Transformation Subjects
Phase II : Richter's transformation subjects who have failed at least one prior therapy
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : Follicular Lymphoma (FL) Subjects
Phase II : Follicular Lymphoma (FL) subjects who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : Mantle Cell Lymphoma (MCL) Subjects
Phase II : Mantle Cell Lymphoma (MCL) subjects who have failed at least 2 prior systemic therapies
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : Marginal Zone Lymphoma (MZL) Subjects
Phase II : Marginal Zone Lymphoma (MZL) subjects who have failed at least 2 prior systemic therapies
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : High-grade B-cell Lymphoma Subjects
Phase II : High-grade B-cell lymphoma subjects who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations
Drug: ARQ 531
ARQ 531 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.

Experimental: Phase II : Waldenström macroglobulinemia (WM) Subjects
Phase II : Waldenström macroglobulinemia (WM) subjects who have failed at least 2 prior systemic therapies
Drug: ARQ 531
ARQ 531 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.

Experimental: Food Effect Cohort: B-cell NHL, CLL/SLL and WM Patients
Food Effect Cohort: B-cell NHL, CLL/SLL and WM patients
Drug: ARQ 531
ARQ 531 will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal), or non-fasted conditions and is available in tablets in strengths of 5 mg or 20 mg.




Primary Outcome Measures :
  1. Phase 1/2 : To determine the recommended Phase 2 dose (RP2D) and schedule of ARQ 531 for treatment of selected subjects with relapsed or refractory hematologic malignancies [ Time Frame: Up to approximately 28 weeks ]
  2. Phase 1/2 : To assess the safety and tolerability of ARQ 531 in selected subjects with relapsed or refractory hematologic malignancies [ Time Frame: Up to approximately 24 weeks ]
    dose. If 2 or more treated subjects at a dose level experience a DLT before Day 29, dose escalation will stop and the prior dose level will be considered the MTD for that schedule.


Secondary Outcome Measures :
  1. Phase 1: Characterization of Pharmacokinetics (Tmax) [ Time Frame: Up to approximately 24 weeks ]
    Time of occurrence for maximum drug concentration (Tmax)

  2. Phase 1: Characterization of Pharmacokinetics (Cmax) [ Time Frame: Up to approximately 24 weeks ]
    Maximum drug concentration (Cmax)

  3. Phase 1: Characterization of Pharmacokinetics (AUC) [ Time Frame: Up to approximately 24 weeks ]
    Area Under the Curve (AUC)

  4. Phase 1: Characterization of Pharmacokinetics (t1/2) [ Time Frame: Up to approximately 24 weeks ]
    Elimination half-life (t1/2)

  5. Phase 2: Preliminary evidence of anti-tumor activity, in terms of Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 weeks ]
  6. Phase 2 : Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) [ Time Frame: Up to approximately 24 weeks ]


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

  1. Signed written informed consent granted prior to initiation of any study-specific procedures.
  2. 18 years of age and older.
  3. For the dose escalation cohorts, relapsed or refractory subjects with a diagnosis of B-cell NHL, CLL/SLL and WM who have received at least two prior systemic therapies . Subjects must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Subjects with low grade lymphoma must be progressing and requiring treatment..
  4. For the expansion cohorts, the following criteria must be met:

    • Cohort A: Relapsed/Refractory (R/R) CLL/SLL subjects with at least 2 prior systemic therapies and previously treated with a covalent BTKi who must have a documented BTK mutation on C481 residue
    • Cohort B: R/R CLL/SLL subjects 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 subjects who have failed at least one prior therapy
    • Cohort D: Follicular Lymphoma (FL) subjects who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A
    • Cohort E: Mantle Cell Lymphoma (MCL) subjects who have failed at least 2 prior systemic therapies
    • Cohort F: Marginal Zone Lymphoma (MZL) subjects who have failed at least 2 prior systemic therapies
    • Cohort G: High-grade B-cell lymphoma subjects who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations
    • Cohort H: Waldenström macroglobulinemia (WM) subjects who have failed at least 2 prior systemic therapies
  5. Disease status requirement:

    1. For CLL subjects, symptomatic disease that mandates treatment (Hallek et al. 2018).
    2. For B-cell NHL subjects, measurable disease by imaging scan.
    3. For WM, serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal (ULN).
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  7. Good organ function

    1. Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation or by 24-hour urine collection.
    2. Total bilirubin ≤ 1.5 x institutional ULN (total bilirubin of ≤ 3 x institutional ULN in subjects with documented Gilbert's syndrome).
    3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN.
    4. Platelet count ≥ 50,000/µL
    5. Absolute neutrophil count (ANC) ≥ 1000/µL.
    6. Hemoglobin (Hgb) ≥ 8.0 g/dL, stable for ≥ 1 week.
  8. 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.
  9. Female subjects of child-bearing potential must have a negative serum pregnancy test within 14 days of the first day of drug dosing.
  10. Ability to swallow oral medications without difficulty.

    Exclusion Criteria

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

  11. 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.
  12. Transformation of FL to a more aggressive subtype of lymphoma or grade 3b FL
  13. Subjects currently being treated with the following drugs:

    1. CYP 2C9 substrates with a narrow therapeutic index (such as warfarin, phenytoin)
    2. CYP 2C8 substrates with a narrow therapeutic index (such as paclitaxel)
    3. CYP 2C19 substrates with a narrow therapeutic index (such as S-mephenytoin)
    4. CYP 2D6 substrates with a narrow therapeutic index (such as thioridazine, pimozide)
    5. 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 subject to be eligible for study enrollment.
  14. Prior allogeneic bone marrow transplant.
  15. Active central nervous system (CNS) involvement.
  16. Pregnant or breast-feeding women.
  17. Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug.
  18. 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.
  19. 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.
  20. Active human immunodeficiency virus (HIV) infection, Hepatitis B, or Hepatitis C infection.
  21. Other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the subject's safety or interfere with the evaluation of the safety of the study agent.
  22. 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


Contacts
Layout table for location contacts
Contact: ArQule, Inc. 781-994-0300 ClinicalTrials@arqule.com

Locations
Layout table for location information
United States, North Carolina
Duke University Health System Recruiting
Durham, North Carolina, United States, 27710
Contact    781-994-0300    ClinicalTrials@arqule.com   
United States, Ohio
Wexner Medical Center at The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact    781-994-0300    ClinicalTrials@arqule.com   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact    781-994-0300    ClinicalTrials@arqule.com   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact    781-994-0300    ClinicalTrials@arqule.com   
United States, Utah
University of Utah, Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact    781-994-0300    ClinicalTrials@arqule.com   
Sponsors and Collaborators
ArQule

Layout table for additonal information
Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT03162536     History of Changes
Other Study ID Numbers: ARQ 531-101
First Posted: May 22, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
ARQ 531
Hematologic Malignancies
SLL
CLL
B-cell NHL
WM
BTK (Bruton's 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
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders