Status:

COMPLETED

Dose Escalation Study of ARQ 621 in Adult Patients With Metastatic Solid Tumors and Hematologic Malignancies

Lead Sponsor:

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

Conditions:

Metastatic Solid Tumors, Refractory/Relapsed Hematologic Malignancies

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

This is an open-label, dose escalation study of intravenous ARQ 621 administered to patients with late-stage solid tumors or hematologic malignancies.

Detailed Description

The study is designed to explore the safety, tolerability and pharmacokinetics of ARQ 621 and define a recommended phase 2 (RP2D)dose of ARQ 621.Treatment will be initiated at a dose level of 10 mg/m\...

Eligibility Criteria

Inclusion

  • Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH)- Good Clinical Practice (GCP), the local regulatory requirements, and permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPPA) prior to study-specific screening procedures
  • A histologically or cytologically confirmed metastatic solid tumor or refractory/relapsed hematologic malignancy
  • Have a life expectancy of at least 12 weeks
  • ≥18 years of age
  • Measurable disease as defined by:
  • Solid Tumors: Response Evaluation Criteria in Solid Tumors
  • Multiple Myeloma (MM): International Uniform Response Criteria, at least one of the following:
  • Monoclonal protein in the plasma of ≥0.5 g/dL
  • Monoclonal protein in the urine of ≥0.2 g/24 hr urine collection
  • Serum immunoglobulin free light chain (FLC) ≥100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa to lambda FLC ratio
  • Malignant Lymphoma (ML): International Working Group Response Criteria
  • At least one site of disease ≥2 cm in longest diameter (a lesion ≥1 cm can be considered if PET positive)
  • Chronic Lymphocytic Leukemia (CLL): NCI Working Group Guidelines
  • Lymphocytosis (5 x 10\^9 /L) with B-cell marker (CD19, CD20,CD23) + CD5
  • High-risk characteristics (hemoglobin \<10g/dL OR platelets \<100 x 10\^9 /L)
  • Acute Myelogenous Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL): only patients with bone marrow or peripheral blast count of ≥20%
  • Acute Promyelocytic Leukemia (APML): patients must be refractory to all-trans retinoic acid (ATRA) and arsenic trioxide
  • Chronic Myelogenous Leukemia (CML): patients in blast crisis (bone marrow or peripheral blast count ≥20%) may be included if refractory to prior therapy and to any therapy the investigators deems of higher priority (for example, BCR-ABL inhibitors such as imatinib mesylate \[Gleevec\], nilotinib \[Tasigna\], or dasatinib \[Sprycel\])
  • ECOG performance status ≤2
  • Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last ARQ 621 dose
  • Females of childbearing potential must have a negative serum pregnancy test
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5.0 × ULN with metastatic liver disease
  • Hemoglobin (Hgb) ≥10 g/dL (except in cases considered related to hematologic malignancy)
  • Total bilirubin ≤1.5 × ULN
  • Creatinine ≤1.5 x ULN (≤2.0 x ULN in cases considered related to multiple myeloma)
  • Absolute neutrophil count ≥1.5 x 10\^9/L (except in cases considered related to hematologic malignancy)
  • Platelets ≥100 x 10\^9/L (except in cases considered related to hematologic malignancy)
  • Patients with hematologic malignancies who have progressed following at least two prior treatment regimens

Exclusion

  • Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of the first dose
  • In cases of hematologic malignancies, 4-week recovery from prior anticancer treatment is not required, however the patient must recover from prior treatment-related non-hematological toxicities to grade 2 or less
  • When required for supportive care corticosteroids or hydroxyurea may be used
  • Surgery within four weeks prior to the first dose
  • Known untreated brain metastases or leptomeningeal disease
  • Patients with solid tumors who were treated for brain metastases and who have shown stable disease for at least 8 weeks prior to enrollment will be allowed
  • Pregnant or breastfeeding
  • Uncontrolled concurrent illness including, but not limited to ongoing or active symptomatic infection requiring systemic therapy, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients having a history of Thrombotic thrombocytopenic purpura (TTP) or Hemolytic-uremic syndrome (HUS) or HUS spectrum will be excluded from the study

Key Trial Info

Start Date :

August 1 2009

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 1 2011

Estimated Enrollment :

50 Patients enrolled

Trial Details

Trial ID

NCT00825487

Start Date

August 1 2009

End Date

September 1 2011

Last Update

October 19 2011

Active Locations (4)

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Page 1 of 1 (4 locations)

1

Translational Genomics Institute

Phoenix, Arizona, United States, 85004

2

Premiere Oncology

Santa Monica, California, United States, 90404

3

Boston, Massachusetts, United States, 02111

4

Nevada Cancer Institute

Las Vegas, Nevada, United States, 89135