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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Prolexys Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Prolexys Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01695590
First received: September 18, 2012
Last updated: May 31, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
Multiple Myeloma
Drug: PRLX 93936
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Prolexys Pharmaceuticals:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Cycle 1 (28 days from first dose) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response to treatment [ Time Frame: Each cycle (assessed every 28 days starting from first dose, for up to 8 months) ] [ Designated as safety issue: No ]
  • Time to response [ Time Frame: From date of first dose to date of response, assessed up to 8 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: From date of first dose to first documented progression, assessed up to 8 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01695590

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

No publications provided

Responsible Party: Prolexys Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01695590     History of Changes
Other Study ID Numbers: PRLX93936-0002
Study First Received: September 18, 2012
Last Updated: May 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Prolexys Pharmaceuticals:
Myeloma
PRLX93936

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

ClinicalTrials.gov processed this record on July 22, 2014