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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Multiple Myeloma

Thank you

Trial Information

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 (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).


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Time Frame:

Cycle 1 (28 days from first dose)

Safety Issue:

Yes

Principal Investigator

Paul Richardson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

PRLX93936-0002

NCT ID:

NCT01695590

Start Date:

March 2012

Completion Date:

September 2014

Related Keywords:

  • Multiple Myeloma
  • Myeloma
  • PRLX93936
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Duke University Medical Center Durham, North Carolina  27710
Dana Farber Cancer Institute Boston, Massachusetts  02115
Tufts Medical Center Boston, Massachusetts  02111
University of Cincinnati Cincinnati, Ohio  45267-0502
University of North Carolina at Chapel Hill Chapel Hill, North Carolina  27599
Sarah Cannon Research Institute Nashville, Tennessee  37203