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

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

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

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: PRLX 93936

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: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Amy Destefanis; Phone Number: 617-632-6752; Email: amyl_destefanis@dfci.harvard.edu
      • Principal Investigator: Robert Schlossman, MD
    • Boston, Massachusetts, United States, 02111
      • Withdrawn
      • Tufts Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Barbara Riff; Phone Number: 919-843-7046; Email: barbara_riff@med.unc.edu
      • Contact: Katherine McKernan; Phone Number: 919-966-4432; Email: katherine_mckernan@med.unc.edu
      • Principal Investigator: Peter Voorhees, MD
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Cristina Gasparetto, MD
      • Contact: Kimberly Oates; Phone Number: 919-668-6524; Email: kimberly.bartlett@duke.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Contact: Sue O'Gara; Phone Number: 513-604-3982; Email: sue.ogara@uc.edu
      • Principal Investigator: John Morris, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: Cindy Farley; Phone Number: 615-329-7237; Email: cindy.farley@scresearch.net
      • Principal Investigator: Jesus G. Berdeja, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Prolexys Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): March 1, 2014
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: September 18, 2012
• First Submitted That Met QC Criteria: September 25, 2012
• First Posted (Estimate): September 28, 2012

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: May 31, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Myeloma; PRLX93936
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: PRLX93936-0002