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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01695590
• Other study ID #: PRLX93936-0002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 18, 2012
• Last updated: May 31, 2013
• Start date: March 2012
• Est. completion date: September 2014

Study information

• Verified date: May 2013
• Source: Prolexys Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Sarah Cannon Research Institute	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Prolexys Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose		Cycle 1 (28 days from first dose)	Yes
Secondary	Response to treatment		Each cycle (assessed every 28 days starting from first dose, for up to 8 months)	No
Secondary	Time to response		From date of first dose to date of response, assessed up to 8 months	No
Secondary	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	No
Secondary	Time to progression		From date of first dose to first documented progression, assessed up to 8 months	No