A Study of ARRY-520 and Bortezomib Plus Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

NCT01248923 | Completed Phase 1

• 1 other identifier: ARRAY-520-111
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 13

Brief Summary

This is a Phase 1 study during which patients with relapsed or refractory multiple myeloma (MM) or plasma cell leukemia (PCL) will receive investigational study drug ARRY-520 and bortezomib, with or without dexamethasone, with granulocyte-colony stimulating factor (G-CSF) support. This study has 2 parts. In the first part, patients will receive increasing doses of study drug (2 dosing schedules will be evaluated) in combination with (1) bortezomib with G-CSF support or (2) bortezomib and dexamethasone with G-CSF support, in order to achieve the highest dose of study drug possible that will not cause unacceptable side effects. Approximately 45 patients from the US will be enrolled in Part 1 (Active, not recruiting). In the second part of this study, patients will receive the best dose(s) and schedule(s) of study drug, in combination with bortezomib ± dexamethasone + G-CSF, determined from the first part of the study and will be followed to see what side effects the combination causes and what effectiveness the combination has, if any, in treating the cancer. Approximately 42 patients from the US will be enrolled in Part 2 (Active, not recruiting).

Conditions

Multiple Myeloma, Plasma Cell Leukemia

Keywords

relapsed multiple myeloma; plasma cell dyscrasia; plasmacytoma; kinesin spindle protein; anti-mitotic

Outcome Measures

Primary Outcomes (3)

• Characterize the safety profile of the study drug in combination with bortezomib ± dexamethasone + G-CSF in terms of adverse events, clinical laboratory tests and electrocardiograms.

  Part 1

• Establish the maximum tolerated dose (MTD) of the study drug in combination with bortezomib ± dexamethasone + G-CSF.

  Part 1

• Assess the efficacy of study drug in combination with bortezomib ± dexamethasone + G-CSF in terms of best overall response

  Part 2

Secondary Outcomes (3)

• Assess the efficacy of study drug in combination with bortezomib ± dexamethasone + G-CSF in terms of duration of response, time to progression, treatment-free interval and time to next treatment.

  Part 1 and Part 2

• Characterize the safety profile of the study drug in combination with bortezomib ± dexamethasone + G-CSF in terms of adverse events, clinical laboratory tests and electrocardiograms.

  Part 2

• Assess the pharmacokinetic (PK) drug interactions between ARRY-520 and bortezomib in terms of plasma concentration-time profiles.

  Part 2

Study Arms (3)

ARRY-520 (Schedule 1) + bortezomib + G-CSF

EXPERIMENTAL

Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous

ARRY-520 (Schedule 1) + bortezomib + dexamethasone + G-CSF

EXPERIMENTAL

Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous; Drug: Dexamethasone, steroid; oral; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous

ARRY-520 (Schedule 2) + bortezomib + dexamethasone + G-CSF

EXPERIMENTAL

Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous; Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous; Drug: Dexamethasone, steroid; oral; Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous

Interventions

ARRY-520, KSP(Eg5) inhibitor; intravenous DRUG

Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule.

ARRY-520 (Schedule 1) + bortezomib + dexamethasone + G-CSF; ARRY-520 (Schedule 2) + bortezomib + dexamethasone + G-CSF

Bortezomib, proteasome inhibitor; intravenous or subcutaneous DRUG

Part 1: standard of care; Part 2: standard of care determined in Part 1.

ARRY-520 (Schedule 1) + bortezomib + dexamethasone + G-CSF; ARRY-520 (Schedule 2) + bortezomib + dexamethasone + G-CSF

Dexamethasone, steroid; oral DRUG

Part 1: standard of care; Part 2: standard of care determined in Part 1.

ARRY-520 (Schedule 1) + bortezomib + dexamethasone + G-CSF; ARRY-520 (Schedule 2) + bortezomib + dexamethasone + G-CSF

Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous DRUG

Part 1: standard of care; Part 2: standard of care.

ARRY-520 (Schedule 1) + bortezomib + dexamethasone + G-CSF; ARRY-520 (Schedule 2) + bortezomib + dexamethasone + G-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed relapsed or refractory MM (measurable disease) or PCL.
• Prior treatment regimens for Part 1: Patients should have received at least 2 prior treatment regimens. Prior treatment must have included at least one full cycle of a proteasome inhibitor (e.g., bortezomib or carfilzomib) and at least one full cycle of an IMiD (e.g., thalidomide, lenalidomide or pomalidomide).
• Prior treatment regimens for Part 2: Patients should have received 1 to 3 prior treatment regimens. Prior treatment could have included bortezomib only if the disease was not refractory to treatment with bortezomib (refractory defined as documented progression on therapy or within 60 days of completing treatment with bortezomib).
• The disease should have progressed per IMWG criteria during or after the last prior treatment regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate hematology laboratory values without transfusion support and without hematological growth factor support within 2 weeks of screening.
• Adequate liver and renal function.
• Additional criteria exist.

You may not qualify if:

• Primary amyloidosis.
• Peripheral neuropathy ≥ Grade 2 or neuropathy with pain, regardless of grade.
• 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.
• Treatment with an investigational medicinal product or device within 28 days 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).
• Major surgery within 14 days and minor surgery within 7 days prior to first dose of study drug.
• Corticosteroid doses \> 10 mg/day of prednisone or equivalent within 14 days 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.

Sponsors & Collaborators

• Array Biopharma, now a wholly owned subsidiary of Pfizer: lead

Study Sites (13)

Clearview Cancer Institute

Huntsville, Alabama, 35805, United States

Location

Arizona Clinical Research Center, Inc.

Tucson, Arizona, 85715, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Associates in Oncology/Hematology

Rockville, Maryland, 20850, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

NYU Cancer Center

New York, New York, 10016, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Charleston Hematology Oncology Associates

Charleston, South Carolina, 29414, United States

Location

The Jones Clinic

Germantown, Tennessee, 38138, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37212, United States

Location

Baylor Charles A. Sammons Cancer Center at Dallas

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Plasma Cell; Paraproteinemias; Plasmacytoma

Interventions

filanesib; Bortezomib; Proteasome Inhibitors; Injections, Subcutaneous; Dexamethasone; Steroids; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2010
• First Posted: November 25, 2010
• Study Start: December 1, 2010
• Primary Completion: March 1, 2016
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

US (13)