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

NCT00821249 | Completed Phase 1

• 1 other identifier: ARRAY-520-212
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

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).

Conditions

Multiple Myeloma; Plasma Cell Leukemia

Keywords

plasma cell dyscrasia; plasmacytoma; kinesin spindle protein; anti-mitotic

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (3)

ARRY-520

EXPERIMENTAL

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

ARRY-520 + G-CSF support

EXPERIMENTAL

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

ARRY-520 + dexamethasone + G-CSF support

EXPERIMENTAL

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

Interventions

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

Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule; Part 3: multiple dose, single schedule.

ARRY-520; ARRY-520 + G-CSF support; ARRY-520 + dexamethasone + G-CSF support

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

Part 1: standard of care; Part 2: standard of care; Part 3: standard of care.

ARRY-520 + G-CSF support; ARRY-520 + dexamethasone + G-CSF support

Dexamethasone, steroid; oral DRUG

Part 3: standard of care.

ARRY-520 + dexamethasone + G-CSF support

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (5)

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 28817190 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Plasma Cell; Paraproteinemias; Plasmacytoma

Interventions

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

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)

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; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

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: January 9, 2009
• First Posted: January 13, 2009
• Study Start: January 1, 2009
• Primary Completion: March 16, 2016
• Study Completion: March 16, 2016
• Last Updated: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

US (5)