Clinical Trials /

A Phase 1/2a Dose-Finding Study of PT-112 in Patients With Relapsed or Refractory Multiple Myeloma

NCT03288480

Description:

Study PT-112-102, a multicenter, open-label dose-finding and pharmacokinetic study of PT-112 in patients with relapsed or refractory multiple myeloma. This is designed as a two-part study. In the first part of the study, cohorts of three patients (expanded to six patients in the event of a dose-limiting toxicity) will receive escalating doses of PT-112 until the MTD is reached, based on tolerability observed during the first 28 days of treatment. In the second part of the study, an expansion cohort of 14 patients will be treated at the recommended dose to confirm the tolerability of treatment and evaluate evidence of treatment efficacy.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1/2a Dose-Finding Study of PT-112 in Patients With Relapsed or Refractory Multiple Myeloma
  • Official Title: A Phase 1/2a Dose-Finding Study of PT-112 in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: PT-112-102
  • NCT ID: NCT03288480

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
PT-112PT-112

Purpose

Study PT-112-102, a multicenter, open-label dose-finding and pharmacokinetic study of PT-112 in patients with relapsed or refractory multiple myeloma. This is designed as a two-part study. In the first part of the study, cohorts of three patients (expanded to six patients in the event of a dose-limiting toxicity) will receive escalating doses of PT-112 until the MTD is reached, based on tolerability observed during the first 28 days of treatment. In the second part of the study, an expansion cohort of 14 patients will be treated at the recommended dose to confirm the tolerability of treatment and evaluate evidence of treatment efficacy.

Trial Arms

NameTypeDescriptionInterventions
PT-112OtherThis is a single arm study of PT-112, which is administered to patients with relapsed or refractory MM
  • PT-112

Eligibility Criteria

        Key Inclusion Criteria:

          1. Previously diagnosed with MM requiring treatment based on IMWG diagnostic criteria;

          2. Relapsed or refractory MM after adequate exposure to and therapeutic response
             (following IMWG response criteria) to at least one line of treatment with one or more
             active agents, including alkylating drugs, corticosteroids, immunomodulatory drugs
             (IMiD: thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib,
             cartilzomib), and monoclonal antibodies (daratumumab, elotuzumab, ixazomab);

          3. Evaluable MM with at least one of the following: (a) serum monoclonal component ≥ 0.5
             g/dL; or (b) Bence Jones (BJ) proteinuria ≥ 200 mg/24h; or (c) measurable plasmacytoma
             (not previously irradiated); or (d) involved serum free light chain ≥ 10 mg/dL with an
             abnormal free light chain ratio;

          4. ECOG Performance Status (PS) 0-2;

          5. Life expectancy > 3 months;

          6. At least 2 weeks (or 5 half-lives, whichever is longer) wash-out since the end of
             previously administered experimental therapy (6 weeks if previous nitrosourea
             containing regimen) or 2 weeks for standard-of-care regimens. Concurrent
             corticosteroids are allowed provided they are administered at an equivalent prednisone
             dose of ≤ 10 mg/day, as prediction or blood products only;

          7. Recovery from non-hematologic toxic effects of prior therapy to grade ≤ 1 (except
             alopecia) by NCI CTCAE Version 4.03;

          8. Adequate bone marrow (BM), renal, hepatic and metabolic function.

        Key Exclusion Criteria:

          1. Any of the following concomitant diseases/conditions:

               -  History or presence of myocardial infarction, clinically relevant valvular heart
                  disease, or congestive heart failure within the last 12 months;

               -  Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT
                  interval (QTc) (Fridericia) to >480 msec for males or >500 msec for females,
                  based on ECG at screening (patients with stable atrial fibrillation on treatment
                  are allowed provided they do not meet any other cardiac or prohibited drug
                  exclusion criterion);

               -  Presence of current angina;

               -  Active uncontrolled infection;

               -  Morphological or cytological features of myelodysplasia and/or post-chemotherapy
                  aplasia on BM assessment;

               -  Myopathy > grade 2 or any clinical situation that causes significant and
                  persistent elevation of CPK (>2.5 x ULN in two different determinations performed
                  one week apart);

               -  Peripheral neuropathy > grade 1, except for grade 2 without limitations on
                  instrumental daily life activities;

               -  POEMS syndrome or active plasma cell leukemia;

               -  Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the
                  control of GVHD;

               -  History or presence within the last 3 months of Deep Vein Thrombosis (DVT) or a
                  pulmonary embolism (PE);- Uncontrolled leptomeningeal disease;

               -  Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia);

               -  Acute or chronic infections requiring systemic therapy, including, among others:

               -  active infection requiring systemic therapy;

               -  history of testing positive to human immunodeficiency virus (HIV) or known
                  acquired immunodeficiency syndrome;

               -  hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
                  (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is
                  positive);

               -  active tuberculosis (history of exposure or history of positive TB test with
                  presence of clinical symptoms, physical or radiographic finding);

               -  Any other major illness that, in the Investigator's judgment, may substantially
                  increase the risk associated with the patient's participation in this study;

          2. History of prior malignancy other than those previously treated with a curative intent
             more than 5 years ago and without relapse (any tumor) or basal cell skin cancer, in
             situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps
             treated adequately, regardless of the disease-free interval;

          3. Prior irradiation to > 30% of BM reserves (including total body irradiation),
             regardless of the washout period;

          4. High dose chemotherapy followed by autologous stem cell transplantation within 90 days
             prior to initiating study treatment;

          5. Bisphosphonate treatment within 7 days prior to initiating study treatment (while on
             study, bisphosphonates can be administered only once a month, between Days 18 to 21 of
             the 28-day treatment cycle)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended dose (RD) of PT-112 for further studies in patients with relapsed or refractory multiple myeloma (MM)
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Peak Plasma Concentration (Cmax)
Time Frame:18 months
Safety Issue:
Description:
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:18 months
Safety Issue:
Description:
Measure:Dose-limiting toxicities (DLTs)
Time Frame:18 months
Safety Issue:
Description:
Measure:Number of patients with Adverse Events (AEs)
Time Frame:18 months
Safety Issue:
Description:Characterization of the type, incidence, severity, duration, reversibility and relationship to treatment of adverse events (AEs), and effects on vital signs and laboratory parameters.
Measure:Tumor response, including assessment of minimal residual disease, according to the International Myeloma Working Group (IMWG) response criteria
Time Frame:18 months
Safety Issue:
Description:
Measure:Duration of response
Time Frame:18 months
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:18 months
Safety Issue:
Description:
Measure:Relationship between sensitivity/response to treatment and disease status including cytogenetic biomarkers
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Phosplatin Therapeutics

Last Updated

September 3, 2019