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Arry-520 + Carfilzomib for Multiple Myeloma (MM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Array BioPharma
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01372540
First received: June 10, 2011
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

This study is divided into study groups, as described below. The goal of Groups 1A and 2A of this clinical research study is to find the highest tolerable dose of the combination of ARRY-520 and carfilzomib that can be given to patients with multiple myeloma or plasma cell leukemia.

The goal of Groups 1B and 2B of this study is to learn if the combination of carfilzomib and ARRY-520 can help to control multiple myeloma or plasma cell leukemia. Researchers would also like to learn if ARRY-520 can help carfilzomib to work in patients who have built up a resistance to carfilzomib or carfilzomib alone has not helped to control the disease.

The safety of the study drugs will be studied in all groups.


Condition Intervention Phase
Myeloma
Drug: Arry-520
Drug: Carfilzomib
Drug: Dexamethasone
Drug: Filgrastim
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Arry-520 and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of ARRY-520 With Carfilzomib [ Time Frame: Evaluated with each 28 day cycle ] [ Designated as safety issue: Yes ]
    MTD is the level at which ≥2/6 or ≥2/3 dose limiting toxicities (DLTs) are observed in after completion of one cycle (28 days) of combination therapy.


Estimated Enrollment: 76
Study Start Date: February 2012
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 A: Arry-520 + Carfilzomib
Arry-520 starting dose .75 mg/m^2 intravenous (IV) on Days 1, 2, 15 and 16; Carfilzomib IV 20/27 mg/m^2/day on Days 1 ,2, 8, 9 and 15, 16; and Dexamethasone 4 mg oral/IV on Days 1, 2, 8, 9 and 15, 16.
Drug: Arry-520
Part 1A Starting Dose: .75 mg/m2 by vein on Days 1, 2, 15 and 16.
Drug: Carfilzomib

Part 1A Starting Dose: 20/27 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Part 1B Staring Dose: 20 mg/m2 dosing will be only on cycle 1 days 1 and 2, then starting 20/36 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Dose Expansion Group: MTD of Part A and Part B.

Drug: Dexamethasone
Part 1A and 1B, Part 2A and 2B: 4 mg by mouth or by vein on Days 1, 2, 8, 9 and 15, 16.
Other Name: Decadron
Drug: Filgrastim
under the skin beginning on Day 3 or 4, and Day 17 or 18 of every cycle, and continue 1 time each day for 5-7 days.
Other Names:
  • G-CSF
  • Neupogen
Experimental: 1B Arry-520 MTD + Carfilzomib
Arry-520 MTD IV with dose escalate of Carfilzomib IV starting at 20/36 mg/m^2/day; and Dexamethasone 4 mg oral/IV.
Drug: Arry-520
Part 1A Starting Dose: .75 mg/m2 by vein on Days 1, 2, 15 and 16.
Drug: Carfilzomib

Part 1A Starting Dose: 20/27 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Part 1B Staring Dose: 20 mg/m2 dosing will be only on cycle 1 days 1 and 2, then starting 20/36 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Dose Expansion Group: MTD of Part A and Part B.

Drug: Dexamethasone
Part 1A and 1B, Part 2A and 2B: 4 mg by mouth or by vein on Days 1, 2, 8, 9 and 15, 16.
Other Name: Decadron
Drug: Filgrastim
under the skin beginning on Day 3 or 4, and Day 17 or 18 of every cycle, and continue 1 time each day for 5-7 days.
Other Names:
  • G-CSF
  • Neupogen
Experimental: 2 A: Dose Expansion Group
Arry-520 MTD from 1B + Carfilzomib MTD from 1B; and Dexamethasone 4 mg oral/IV.
Drug: Arry-520
Part 1A Starting Dose: .75 mg/m2 by vein on Days 1, 2, 15 and 16.
Drug: Carfilzomib

Part 1A Starting Dose: 20/27 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Part 1B Staring Dose: 20 mg/m2 dosing will be only on cycle 1 days 1 and 2, then starting 20/36 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Dose Expansion Group: MTD of Part A and Part B.

Drug: Dexamethasone
Part 1A and 1B, Part 2A and 2B: 4 mg by mouth or by vein on Days 1, 2, 8, 9 and 15, 16.
Other Name: Decadron
Drug: Filgrastim
under the skin beginning on Day 3 or 4, and Day 17 or 18 of every cycle, and continue 1 time each day for 5-7 days.
Other Names:
  • G-CSF
  • Neupogen
Experimental: 2B Dose Expansion Group
Arry-520 either at MTD from 1A or one dose level lower; Carfilzomib MTD from 1A; and Dexamethasone 4 mg oral/IV on Days 1, 2, 8, 9 and 15, 16.
Drug: Arry-520
Part 1A Starting Dose: .75 mg/m2 by vein on Days 1, 2, 15 and 16.
Drug: Carfilzomib

Part 1A Starting Dose: 20/27 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Part 1B Staring Dose: 20 mg/m2 dosing will be only on cycle 1 days 1 and 2, then starting 20/36 mg/m2 by vein on Days 1,2 8,9 and 15,16.

Dose Expansion Group: MTD of Part A and Part B.

Drug: Dexamethasone
Part 1A and 1B, Part 2A and 2B: 4 mg by mouth or by vein on Days 1, 2, 8, 9 and 15, 16.
Other Name: Decadron
Drug: Filgrastim
under the skin beginning on Day 3 or 4, and Day 17 or 18 of every cycle, and continue 1 time each day for 5-7 days.
Other Names:
  • G-CSF
  • Neupogen

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Confirmed relapsed or refractory MM or PCL. Patients should have received at least 1 prior treatment regimen. Prior treatment must have included at least one full cycle of a proteasome inhibitor (e.g., bortezomib) and at least one full cycle of an IMiD (e.g., thalidomide, lenalidomide or pomalidomide). Patients who have had prior ARRY-520 and carfilzomib will be allowed in the dose escalation phase, however prior ARRY-520 and carfilzomib will be excluded in the dose expansion cohort 1 of Part A. There will be 2 cohorts in the dose expansion of part A: Cohort 1 will be patients who are carfilzomib sensitive; Cohort 2 will be patients who are carfilzomib refractory.
  2. Continuation of Inclusion Criteria #1: Part B: Once a MTD has been established in Part A, additional dose escalation will occur with subsequent dose escalation of Carfilzomib. During the dose escalation of Part B, pt must have at least 1 line of prior therapy and no limitations on prior therapy. At the MTD of part B, an additional 14 patients will be enrolled at the MTD. Patients who had prior clinical benefit/response to ARRY-520 or Carfilzomib with a stable disease (SD) or better may be eligible for dose expansion of Part B. There will be 2 cohorts in the dose expansion of part B: Cohort 1 will be patients who are carfilzomib sensitive; Cohort 2 will be patients who are carfilzomib refractory.
  3. Measurable MM disease, defined as one of the following: A monoclonal immunoglobulin (Ig) concentration on serum electrophoresis of >/= 0.5 g/dL for an IgG myeloma, >/= 0.1 g/dL for an IgD myeloma or 0.5 g/dL for an IgA myeloma. Measurable urinary light chain secretion by quantitative analysis of >/= 200 mg/24 hours. Involved serum FLC level >/= 10 mg/dL, provided the serum free light chain (FLC) ratio is abnormal. Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis.
  4. Male or female, >/= 18 years of age at time of signing consent.
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2.
  6. Adequate hematology laboratory values without transfusion support and without hematological growth factor support within 2 weeks of Screening: Absolute Neutrophil Count (ANC) >/= 1.5 × 10^9/L. Platelets >/= 75 × 10^9/L. If the bone marrow contains >/= 50% plasma cells, a platelet count of >/= 50 × 10^9/L is allowed.
  7. LVEF >/= 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
  8. Adequate liver and renal function: Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) </= 2.5 × the upper limit of normal (ULN). Bilirubin < 2.0 mg/dL. Serum creatinine </= 2.5 mg/dL or a calculated creatinine clearance of at least 50 mL/min (using the Cockcroft and Gault method).
  9. Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, ( those who are post menopausal for less than 1 year) must have negative serum or urine pregnancy test and agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Male patients, even if surgically sterilized (i.e., status postvasectomy), who: Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR Agree to completely abstain from heterosexual intercourse.
  10. Understand and voluntarily signed informed consent.

Exclusion Criteria:

  1. Primary amyloidosis.
  2. Treatment with an investigational product or device within 21 days of Cycle 1 Day 1.
  3. History of allergic reaction/hypersensitivity to any of the study medications, their analogues or excipients in the various formulations.
  4. Cytotoxic therapy or monoclonal antibodies within 21 days prior to Cycle 1 Day 1.
  5. Radiotherapy within 21 days prior to Cycle 1 Day 1. However, if the radiation portal covered </= 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy.
  6. Major surgery within 14 days and minor surgery within 7 days prior to Cycle 1 Day 1.
  7. Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to Cycle 1 Day 1.
  8. Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study or, in the judgment of the Investigator, would make the patient inappropriate for study participation.
  9. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
  10. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  11. Patients who are eligible for autologous transplantation
  12. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
  13. Myocardial infarction within four months prior to enrollment
  14. Lactating women
  15. Patients with known HIV seropositivity
  16. Patients with active clinical infections
  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: NCT01372540

Contacts
Contact: Jatin J. Shah, MD 713-792-2860

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Jatin J. Shah, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Array BioPharma
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Jatin J. Shah, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01372540     History of Changes
Other Study ID Numbers: 2011-0144, NCI-2011-01120
Study First Received: June 10, 2011
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Relapsed/Refractory Multiple Myeloma
MM
Plasma Cell Leukemia
PCL
Arry-520
Carfilzomib
Dexamethasone
Decadron
Filgrastim
G-CSF
Neupogen

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenograstim
Adjuvants, Immunologic
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on November 23, 2014