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

Sponsor

Array Biopharma, now a wholly owned subsidiary of Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01248923

Collaborator

(none)

Enrollment

Locations

Arms

4.2

Patients Per Site

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma, Plasma Cell Leukemia	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 Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARRY-520 (Schedule 1) + bortezomib + G-CSF	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous Part 1: multiple dose, escalating Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous Part 1: standard of care Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous Part 1: standard of care
Experimental: ARRY-520 (Schedule 1) + bortezomib + dexamethasone + G-CSF	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule. Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous Part 1: standard of care; Part 2: standard of care determined in Part 1. Drug: Dexamethasone, steroid; oral Part 1: standard of care; Part 2: standard of care determined in Part 1. Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous Part 1: standard of care; Part 2: standard of care.
Experimental: ARRY-520 (Schedule 2) + bortezomib + dexamethasone + G-CSF	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule. Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous Part 1: standard of care; Part 2: standard of care determined in Part 1. Drug: Dexamethasone, steroid; oral Part 1: standard of care; Part 2: standard of care determined in Part 1. Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous Part 1: standard of care; Part 2: standard of care.

Arm

Intervention/Treatment

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

Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous

Part 1: multiple dose, escalating

Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous

Part 1: standard of care

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

Part 1: standard of care

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

Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous

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

Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous

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

Drug: Dexamethasone, steroid; oral

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

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

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

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

Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous

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

Drug: Bortezomib, proteasome inhibitor; intravenous or subcutaneous

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

Drug: Dexamethasone, steroid; oral

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

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

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria (Part 1 and Part 2):

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.

Key Exclusion Criteria (Part 1 and Part 2):

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clearview Cancer Institute	Huntsville	Alabama	United States	35805
2	Arizona Clinical Research Center, Inc.	Tucson	Arizona	United States	85715
3	City of Hope	Duarte	California	United States	91010
4	Emory University, Winship Cancer Institute	Atlanta	Georgia	United States	30322
5	Associates in Oncology/Hematology	Rockville	Maryland	United States	20850
6	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
7	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
8	NYU Cancer Center	New York	New York	United States	10016
9	Mount Sinai Medical Center	New York	New York	United States	10029
10	Charleston Hematology Oncology Associates	Charleston	South Carolina	United States	29414
11	The Jones Clinic	Germantown	Tennessee	United States	38138
12	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37212
13	Baylor Charles A. Sammons Cancer Center at Dallas	Dallas	Texas	United States	75246