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A Phase 1 Dose Escalation Study of ARQ 621 in Adult Patients With Metastatic Solid Tumors and Hematologic Malignancies

Phase 1
18 Years
Not Enrolling
Metastatic Solid Tumors, Refractory/Relapsed Hematologic Malignancies

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Trial Information

A Phase 1 Dose Escalation Study of ARQ 621 in Adult Patients With Metastatic Solid Tumors and Hematologic Malignancies

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^2 IV infusion for an hour once weekly in 4-week (28 day) consecutive and
continuous cycles. ARQ 621 should be infused IV over two hours at doses 200 mg/m^2 and
higher (cohort 8 and above). All cycles of therapy will consist of the patient taking ARQ
621 intravenously once weekly for 4 weeks. Dose escalation will proceed initially by
doubling (cohorts 2 and 3) and subsequently by a modified Fibonacci scheme. Dose
escalations will be performed using 3-6 patient cohorts. In these cohorts, if a single dose
limiting toxicity (DLT) is experienced among patients 1-3, the dose cohort will be expanded
to six patients. The maximum tolerated dose (MTD) will be defined as the dose level at
which no greater than 1/6 patients experiences a DLT. Once an MTD is identified, up to an
additional 20 patients (with types of malignancy to be determined at a later date by study
investigator and clarified by study amendment) may be treated at this MTD of ARQ 621. If an
MTD is not identified in the initial 10 dosing cohorts, dose escalation will proceed in a
manner to be defined by subsequent amendment with the purpose of determining a RP2D of ARQ

Inclusion Criteria:

- 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

- 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

- Patients with hematologic malignancies who have progressed following at least two
prior treatment regimens

Exclusion Criteria:

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety, tolerability and recommended Phase 2 dose (RP2D) of ARQ 621 administered intravenously.

Outcome Time Frame:

24 months estimated

Safety Issue:



United States: Food and Drug Administration

Study ID:

ARQ 621-101



Start Date:

August 2009

Completion Date:

September 2011

Related Keywords:

  • Metastatic Solid Tumors, Refractory/Relapsed Hematologic Malignancies
  • metastatic
  • hematologic
  • malignancy
  • multiple
  • myeloma
  • malignant
  • lymphoma
  • chronic
  • lymphocytic
  • leukemia
  • acute
  • myelogenous
  • promyelocytic
  • dose escalation
  • safety
  • tolerability
  • pharmacodynamics
  • tumor
  • PK
  • Neoplasms
  • Hematologic Neoplasms



Boston, Massachusetts  
Nevada Cancer Institute Las Vegas, Nevada  89135
Premiere Oncology Santa Monica, California  90404
Translational Genomics Institute Phoenix, Arizona  85004