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

Tracking Information
First Submitted Date ICMJE	September 18, 2012
First Posted Date ICMJE	September 28, 2012
Last Update Posted Date	June 4, 2013
Study Start Date ICMJE	March 2012
Estimated Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 25, 2012)	Maximum Tolerated Dose [ Time Frame: Cycle 1 (28 days from first dose) ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01695590 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 25, 2012)	Response to treatment [ Time Frame: Each cycle (assessed every 28 days starting from first dose, for up to 8 months) ]; Time to response [ Time Frame: From date of first dose to date of response, assessed up to 8 months ]; Duration of response [ Time Frame: 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 [ Time Frame: From date of first dose to first documented progression, assessed up to 8 months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety, Efficacy and Pharmacokinetic Study of PRLX 93936 in Patients With Multiple Myeloma
Official Title ICMJE	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
Brief Summary	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	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).
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Multiple Myeloma
Intervention ICMJE	Drug: PRLX 93936; 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
Study Arms	Experimental: PRLX 93936; PRLX 93936 administered IV 3 days a week (Monday, Wednesday and Friday) for 3 weeks followed by a 9 day rest period = 1 cycle; Intervention: Drug: PRLX 93936
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: September 25, 2012)	40
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	September 2014
Estimated Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01695590
Other Study ID Numbers ICMJE	PRLX93936-0002
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Prolexys Pharmaceuticals
Study Sponsor ICMJE	Prolexys Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
PRS Account	Prolexys Pharmaceuticals
Verification Date	May 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP