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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Array BioPharma
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01248923
First received: November 24, 2010
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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 (Recruiting).


Condition Intervention 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
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Array BioPharma:

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. [ Time Frame: Part 1 ] [ Designated as safety issue: Yes ]
  • Establish the maximum tolerated dose (MTD) of the study drug in combination with bortezomib ± dexamethasone + G-CSF. [ Time Frame: Part 1 ] [ Designated as safety issue: Yes ]
  • Assess the efficacy of study drug in combination with bortezomib ± dexamethasone + G-CSF in terms of best overall response [ Time Frame: Part 2 ] [ Designated as safety issue: No ]

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. [ Time Frame: Part 1 and Part 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Part 2 ] [ Designated as safety issue: Yes ]
  • Assess the pharmacokinetic (PK) drug interactions between ARRY-520 and bortezomib in terms of plasma concentration-time profiles. [ Time Frame: Part 2 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: December 2010
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01248923

Locations
United States, Alabama
Clearview Cancer Institute Recruiting
Huntsville, Alabama, United States, 35805
Contact: Avitra Bone, RN    256-705-4283    avitrab@ccihsv.com   
United States, Arizona
Arizona Clinical Research Center, Inc. Recruiting
Tucson, Arizona, United States, 85715
Contact: Jarret Schonbrun    520-290-2510    jschonbrun@acrcresearch.com   
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Myo Htut, MD    626-256-4673 ext 65285    mhtut@coh.org   
United States, Georgia
Emory University, Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Michelle Godwin    404-778-5127    michelle.godwin@emory.edu   
United States, Maryland
Associates in Oncology/Hematology Recruiting
Rockville, Maryland, United States, 20850
Contact: Mikhail Kalnitskiy    240-826-2116      
United States, Michigan
University of Michigan Comprehensive Cancer Center Terminated
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Silva Lalo Pregja, MBA    313-576-8673    lalos@karmanos.org   
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Lisa La    212-241-8615    Lisa.la@mssm.edu   
NYU Cancer Center Recruiting
New York, New York, United States, 10016
Contact: Sara Marcus    646-501-7921    sara.marcus@nyumc.org   
Contact: Amitabha Mazumder, MD    212-731-5757    amitabha.mazumder@nyumc.org   
United States, South Carolina
Charleston Hematology Oncology Associates Recruiting
Charleston, South Carolina, United States, 29414
Contact: Deborah McNeal, RN, OCN    843-266-2540      
United States, Tennessee
The Jones Clinic Recruiting
Germantown, Tennessee, United States, 38138
Contact: Lori J. Lynch    901-685-5969 ext 322    llynch@jonescancerclinic.com   
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: Clinical Trials Information Program    800-811-8480      
United States, Texas
Baylor Charles A. Sammons Cancer Center at Dallas Recruiting
Dallas, Texas, United States, 75246
Contact: Erica Goetz, RN, BSN    214-818-8325    erica.goetz@baylorhealth.edu   
Sponsors and Collaborators
Array BioPharma
  More Information

No publications provided

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01248923     History of Changes
Other Study ID Numbers: ARRAY-520-111
Study First Received: November 24, 2010
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Array BioPharma:
relapsed multiple myeloma
plasma cell dyscrasia
plasmacytoma
kinesin spindle protein
anti-mitotic

Additional relevant MeSH terms:
Leukemia, Plasma Cell
Leukemia
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Lenograstim
Proteasome Inhibitors
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014