Clinical trial NCT01695590: Safety, Efficacy and Pharmacokinetic Study of PRLX 93936 in Patients With Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Myeloma
PRLX93936
Lead sponsor: Prolexys Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-09-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: Cycle 1 (28 days from first dose)
Secondary outcomes:
measure: Response to treatment
timeFrame: Each cycle (assessed every 28 days starting from first dose, for up to 8 months)
measure: Time to response
timeFrame: From date of first dose to date of response, assessed up to 8 months
measure: Duration of response
timeFrame: 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
measure: Time to progression
timeFrame: From date of first dose to first documented progression, assessed up to 8 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Paul Richardson, MD
role: PRINCIPAL_INVESTIGATOR
References: