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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00821249

Collaborator

(none)

Enrollment

Locations

Arms

86.4

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Plasma Cell Leukemia	Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous Drug: Dexamethasone, steroid; oral	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Actual Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Mar 16, 2016

Actual Study Completion Date :

Mar 16, 2016

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University, Winship Cancer Institute	Atlanta	Georgia	United States	30322
2	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
4	MD Anderson Cancer Center	Houston	Texas	United States	77030
5	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109