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Filanesib (ARRY-520) in Combination With Pomalidomide and Dexamethasone for Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients

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ClinicalTrials.gov Identifier: NCT02384083
Recruitment Status : Active, not recruiting
First Posted : March 10, 2015
Last Update Posted : December 11, 2018
Sponsor:
Collaborators:
Array BioPharma
Celgene Corporation
Information provided by (Responsible Party):
PETHEMA Foundation

Brief Summary:
Phase I/II, Multicenter, Open Label, Clinical Trial to evaluate safety and efficacy and determine the Maximum Tolerated Dose (MTD) of Filanesib in combination with pomalidomide and dexamethasone in relapsed/refractory (R/R) Multiple Myeloma (MM) patients

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Filanesib, pomalidomide and dexamethasone Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II, Multicenter, Open Label, Clinical Trial of Filanesib (ARRY-520) in Combination With Pomalidomide and Dexamethasone for Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients
Actual Study Start Date : September 2015
Actual Primary Completion Date : February 2018
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Filanesib, pomalidomide and dexamethasone
28-day cycles of Filanesib administered iv as a 1-hour (± 10-minute) infusion at escalating doses on days 1, 2, 15 & 16, + pomalidomide administered p.o. at escalating doses during 21 days with 7 days rest period + dexamethasone at a fixed dose of 40 mg po days 1, 8, 15 & 22
Drug: Filanesib, pomalidomide and dexamethasone
Patients will be treated with 28-day cycles of Filanesib administered iv as a 1-hour (± 10-minute) infusion at escalating doses on days 1, 2, 15 & 16, + pomalidomide administered p.o. at escalating doses during 21 days with 7 days rest period + dexamethasone at a fixed dose of 40 mg po days 1, 8, 15 & 22. G-CSF prophylaxis is mandatory in all patients after Filanesib, starting from Day 3 and Day 17 (for a total of 7 days each). Treatment will be continued until progression or unacceptable toxicity.




Primary Outcome Measures :
  1. Maxim Tolerability Dose measured by common toxicity criteria v4.0 [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Eficcacy measured by the rate of responses [ Time Frame: 6 months ]
    Efficacy of the Kinesin Spindle Protein (KSP) inhibitor Filanesib (ARRY-520) in combination with pomalidomide + dexamethasone in relapsed or refractory MM patients.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years.
  • Performance status (ECOG) ≤ 2.
  • Patient is, in the Investigator's opinion, willing and able to comply with the protocol requirements.
  • Patient has given voluntary written Informed Consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Patients previously diagnosed with MM according to the IMWG Criteria (Blood 2011) that after previous treatment with at least 2 regimens require therapy due to a relapse/progression of the disease.
  • Regarding the disease history, patient must:

    • Have received 2 prior lines of therapy including bortezomib and lenalidomide.
    • Be refractory or intolerant to lenalidomide.
    • Be refractory to the last line of therapy.
    • Refractoriness to any therapy is defined as either failure to achieve minimal response with it, or development of progressive disease (PD) while on therapy or within 60 days after finishing it.
    • At least two cycles of treatment must have been received, unless PD is documented earlier.
  • Only for the Phase II, patients must have measurable disease, defined as any of the following:

    • Serum monoclonal protein value ≥ 500 mg/dl.
    • Urine light chain excretion ≥ 200 mg/24 hours.
    • Abnormal serum free light chains (FLCs) ratio plus involved FLC level ≥ 10 mg/dl.

Exclusion Criteria:

  • Prior therapy with Filanesib or pomalidomide.
  • Non-adequate hematological or biochemical parameters as specified below:
  • Hemoglobin < 8.0 g/dl.
  • Platelets count < 75 x109/L without previous platelet transfusions in the last 7 days. If high bone marrow infiltration (>50%) is present, ≥ 50 x109/L platelet count is required.
  • Neutrophils (ANC) <1.5 × 109/L without growth factor support (defined as no growth factor administration for at least 14 days prior to observation). If the bone marrow contains ≥ 50% plasma cells, a neutrophil count ≥1.0 × 109/L is allowed.
  • Aspartate transaminase (AST): > 2.5 x the upper limit range.
  • Alanine transaminase (ALT): > 2.5 x the upper limit range.
  • Total bilirubin: > 2 x the upper limit range.
  • Creatinine clearance: < 45 mL/min (measured or calculated with the Cockcroft and Gault formula).
  • Absence of recovery from any significant non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.
  • Concomitant anti-myeloma therapy, including corticosteroids at a dose greater than 10 mg/d prednisone or equivalent, within 14 days prior to Day 1 of Cycle 1.
  • Pregnant or lactating women; men and women of reproductive potential who are not using highly effective contraceptive methods.
  • Previous history of any other malignancy in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site).
  • Prior allogeneic bone marrow transplantation in the six prior months or active GVHD in the past month prior to cycle 1, day 1.
  • Other relevant diseases or adverse clinical conditions:
  • Congestive heart failure or unstable angina pectoris, myocardial infarction within 12 months before inclusion in the study.
  • Uncontrolled arterial hypertension or unstable cardiac arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).
  • History of significant neurological or psychiatric disorders.
  • Active infection.
  • Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
  • Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
  • Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive or active hepatitis C infection.
  • Limitation of the patient's ability to comply with the treatment or follow-up protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02384083


Locations
Spain
Instoitut Català d'Oncologia
Badalona, Spain, 08916
Hospital Clinico Universitario
Barcelona, Spain, 08036
Hospital Doce de Octubre
Madrid, Spain, 28041
Hospital Morales Messeguer
Murcia, Spain, 30008
Clínica Universitaria de Navarra
Pamplona, Spain, 31008
Hoapital Clinico Universitario Salamanca
Salamanca, Spain, 37007
Hospital General de Segovia
Segovia, Spain, 40002
Hospital Virgen del Rocío
Sevilla, Spain, 41013
Hospital Universitario Dr Peset
Valencia, Spain, 46017
Hospital Lozano Blesa
Zaragoza, Spain, 50009
Sponsors and Collaborators
PETHEMA Foundation
Array BioPharma
Celgene Corporation
Investigators
Principal Investigator: Ocio Enrique, DR PETHEMA Foundation

Publications of Results:

Other Publications:
Lonial S, Shah JJ, Zonder J, Bensinger WI, Cohen AD, Kaufman JL, et al. Prolonged Survival and Improved Response Rates With ARRY-520 In Relapsed/Refractory Multiple Myeloma (RRMM) Patients With Low α-1 Acid Glycoprotein (AAG) Levels: Results From a Phase 2 Study. Blood. 2013;122(21):285-
Shah JJ, Thomas S, Weber DM, Wang M, Orlowski R. Phase 1 Study Of The Novel Kinesin Spindle Protein Inhibitor Arry-520 + Carfilzomib(Car) In Patients With Relapsed And/Or Refractory Multiple Myeloma (RRMM). Haematologica. 2013;98(S1):Abstract-S579
Humphries MJ, Anderson D, Williams L, Rieger R, Tunquist B, Walker D. ARRY-520 Combined With Pomalidomide Displays Enhanced Anti-Tumor Activity In Preclinical Models Of Multiple Myeloma. Blood. 2013;122(21):3167

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT02384083     History of Changes
Other Study ID Numbers: POMDEFIL
First Posted: March 10, 2015    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: January 2018

Keywords provided by PETHEMA Foundation:
Multiple Myeloma
Pethema
Filanesib
Pomalidomide

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Pomalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents