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

• Status: Completed
• Trial end date: 2020-03-23
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation
• Collaborators: Array BioPharma; Celgene Corporation
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Filanesib; Pomalidomide; Thalidomide

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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.