A Study of ARRY-520 in Patients With Relapsed or Refractory Multiple Myeloma

This is a 2-phase study during which patients with relapsed or refractory multiple myeloma (MM) or plasma cell leukemia (PCL), who have already received at least two previous treatments, will receive investigational study drug ARRY-520.

The study has 3 parts. In the first part of the study, Phase 1, patients will receive increasing doses of study drug, with or without granulocyte-colony stimulating factor (G-CSF) support, in order to achieve the highest dose possible that will not cause unacceptable side effects. Approximately 30 patients from the US will be enrolled in Part 1 (Active, not recruiting).

In the second part of the study, Phase 2, patients will receive the best dose of study drug determined from the first part of the study and will be followed to evaluate what side effects the study drug causes and what effectiveness it has, if any, in treating the cancer. Approximately 30 patients from the US will be enrolled in Part 2 (Active, not recruiting).

In the third part of the study, Phase 2 with Dexamethasone, patients will receive the best dose of the study drug determined from the first part of the study, in combination with dexamethasone, and will be followed to evaluate what side effects the combination causes and what effectiveness the combination has, if any, in treating the cancer. Approximately 50 patients from the US will be enrolled in Part 3 (Active, not recruiting).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Plasma Cell Leukemia
• Intervention / Treatment: Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous; Drug: Dexamethasone, steroid; oral

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University, Winship Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria (Part 3):

• Patients should have received at least two prior treatment regimens.
• Confirmed refractory MM (measurable disease) or PCL. Patients must be refractory to treatment with both lenalidomide/dexamethasone and bortezomib/dexamethasone (or to treatment with bortezomib/lenalidomide/dexamethasone), defined as documented progressive disease on therapy or within 60 days of completing treatment with these regimens.
• Previously received adequate alkylator therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate hematology laboratory values without transfusion support within 2 weeks of screening.
• Adequate liver and renal function.
• Additional criteria exist.

Key Exclusion Criteria (Part 3):

• Primary amyloidosis.
• Concomitant malignancies or previous malignancies with less than a 3-year disease free interval at the time of enrollment (patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or Stage A low grade prostate cancer may enroll irrespective of the time of diagnosis).
• Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to first dose of study drug.
• Cytotoxic therapy or monoclonal antibodies within 21 days prior to first dose of study drug.
• Radiotherapy within 21 days prior to first dose of study drug (if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy).
• Corticosteroid doses > 10 mg/day of prednisone or equivalent within 2 weeks prior to first dose of study drug.
• Known positive serology for the human immunodeficiency virus (HIV), hepatitis B and/or active hepatitis C.
• Additional criteria exist.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARRY-520	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule; Part 3: multiple dose, single schedule.
Experimental: ARRY-520 + G-CSF support	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule; Part 3: multiple dose, single schedule.; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous; Part 1: standard of care; Part 2: standard of care; Part 3: standard of care.
Experimental: ARRY-520 + dexamethasone + G-CSF support	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule; Part 3: multiple dose, single schedule.; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous; Part 1: standard of care; Part 2: standard of care; Part 3: standard of care.; Drug: Dexamethasone, steroid; oral; Part 3: standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Establish the maximum tolerated dose (MTD) of study drug, with and without G-CSF.	Part 1
Assess the efficacy of the study drug, with and without dexamethasone, in terms of response rate.	Part 2 and Part 3
Characterize the safety profile of the study drug in combination with dexamethasone in terms of adverse events, clinical laboratory tests and electrocardiograms.	Part 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterize the pharmacokinetics of the study drug.	Part 1
Assess the efficacy of the study drug in terms of response rate, duration of response, progression-free survival, treatment-free survival and time to next treatment.	Part 1
Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.	Part 2
Assess the efficacy of the study drug, with and without dexamethasone, in terms of duration of response, progression-free survival, treatment-free survival, time to next treatment and overall survival.	Part 2 and Part 3
Explore potential biomarkers for pharmacodynamics (PD) and for patient selection.	Part 1, Part 2 and Part 3

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Shah JJ, Kaufman JL, Zonder JA, Cohen AD, Bensinger WI, Hilder BW, Rush SA, Walker DH, Tunquist BJ, Litwiler KS, Ptaszynski M, Orlowski RZ, Lonial S. A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma. Cancer. 2017 Dec 1;123(23):4617-4630. doi: 10.1002/cncr.30892. Epub 2017 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): March 16, 2016
• Study Completion (Actual): March 16, 2016

Study Registration Dates

• First Submitted: January 9, 2009
• First Submitted That Met QC Criteria: January 12, 2009
• First Posted (Estimate): January 13, 2009

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 8, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: plasma cell dyscrasia; plasmacytoma; kinesin spindle protein; anti-mitotic
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Adjuvants, Immunologic; Dexamethasone; Lenograstim; Filanesib
• Other Study ID Numbers: ARRAY-520-212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.