Safety, Efficacy and Pharmacokinetic Study of PRLX 93936 in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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To determine the maximum tolerated dose of, and response to, PRLX 93936 as treatment for patients with relapsed or relapsed/refractory multiple myeloma.

Detailed Description
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To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of PRLX 93936 administered IV 3 days a week (Monday, Wednesday and Friday) for 3 weeks followed by a 9 day rest period, as treatment for patients with relapsed or relapsed/refractory multiple myeloma. To establish the dose of PRLX 93936 recommended for future studies. To characterize potential toxicities of PRLX 93936. To assess the pharmacokinetic profile of PRLX 93936. To evaluate response to treatment, time to response (TTR) and duration of response. To evaluate time to progression (TTP).

Official Title
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Phase 1/2, Multi-center, Open Label, Dose Escalation, Safety, Efficacy and PK Study of PRLX 93936 Administered IV 3 Days a Week for 3 Weeks Followed by a 9 Day Rest Period in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: PRLX 93936


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have a diagnosis of multiple myeloma and have relapsed or relapsed/refractory disease. Patient must have received ≥ 2 prior anti-myeloma regimens including a proteasome inhibitor and/or immunomodulatory agent. Patient currently requires systemic therapy. Patient has measurable disease. Age ≥ 18 years Karnofsky performance status ≥ 60% ECOG performance 0, 1 or 2 Life expectancy of at least three months Able to take acetaminophen Not pregnant Patient must have recovered from toxicities incurred as a result of any previous anti-myeloma therapy or recovered to baseline. Patients who received an autologous stem cell transplant must be ≥ 3 months post-transplant and all associated toxicities must have resolved to ≤ CTCAE Grade 1. QT intervals of QTc ≤ 500 msec Exclusion Criteria: POEMS syndrome Plasma cell leukemia Primary amyloidosis Patient has smoldering multiple myeloma or monoclonal gammopathy of unknown significance (MGUS). Evidence of spinal cord compression or CNS complication unless controlled by appropriate therapy. Patient received chemotherapy or other anti-cancer therapy that may be active against multiple myeloma within 3 weeks prior to the first dose of PRLX 93936. Patient received nitrosureas within 6 weeks prior to the first dose. Patient received corticosteroids within 2 weeks prior to the first dose. Patient received plasmapheresis within 4 weeks prior to the first dose. Patient had major surgery within 4 weeks prior to the first dose. Patient had an allogeneic stem cell transplant within 6 months before first dose of PRLX 93936 or has evidence of graft versus host disease. Patient is taking any therapy concomitantly that may be active against multiple myeloma. Patient is currently receiving medication(s) that are principally metabolized via the cytochrome P450 3A4 enzyme pathway. Use of any investigational agents within 28 days or 5 half-lives (whichever is shorter) of study treatment. Patient has peripheral neuropathy of Grade 3 or greater intensity, or painful Grade 2, as defined by the NCI CTC. Patient had a myocardial infarction within 6 months of enrollment or has NYHA Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Abnormal LVEF (< LLN for the institution for a patient of that age) on echocardiogram Patient has poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to protocol. Patient had a malignancy other than multiple myeloma within 3 years before enrollment, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, or in situ prostate cancer. Patient's clinical laboratory values meet any of the following criteria within the 7 days prior to Study Day 1: Bilirubin > 1.5 times ULN AST (SGOT), ALT (SGPT) and Alkaline phosphatase > 2.5 times ULN Uncontrolled hypercalcemia (defined as serum calcium > 14 mg/dL) Serum creatinine > 2.0 mg/dL or creatinine clearance of < 30 mL/min ANC < 1000 cells/mm3 or < 750 cells/mm3 due to >50% marrow involvement Platelet count < 50,000 cells/mm3 Hemoglobin < 8.0 g/dL Patient is known to be human immunodeficiency virus (HIV)-positive. Patient is known to be hepatitis B surface antigen-positive or has known active hepatitis C infection. Patient has an active systemic infection requiring treatment or within 14 days before first dose of PRLX 93936. Pregnant or nursing women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRLX 93936<br>PRLX 93936 administered IV 3 days a week (Monday, Wednesday and Friday) for 3 weeks followed by a 9 day rest period = 1 cycle | Drug: PRLX 93936<br>* PRLX 93936 administered IV 3 days a week (Monday, Wednesday and Friday) for 3 weeks followed by a 9 day rest period = 1 cycle, multiple cycles may be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | Cycle 1 (28 days from first dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment |  | Each cycle (assessed every 28 days starting from first dose, for up to 8 months) | 
| Time to response |  | From date of first dose to date of response, assessed up to 8 months | 
| Duration of response |  | From date of response to first documented progression or death, or date last known progression-free and alive at study discontinuation, assessed up to 8 months | 
| Time to progression |  | From date of first dose to first documented progression, assessed up to 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloma, PRLX93936