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

NCT03288480 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PT-112-102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Recommended dose (RD) of PT-112 for further studies in patients with relapsed or refractory multiple myeloma (MM)

  18 months

Secondary Outcomes (8)

• Peak Plasma Concentration (Cmax)

  18 months

• Area under the plasma concentration versus time curve (AUC)

  18 months

• Dose-limiting toxicities (DLTs)

  18 months

• Number of patients with Adverse Events (AEs)

  18 months

• Tumor response, including assessment of minimal residual disease, according to the International Myeloma Working Group (IMWG) response criteria

  18 months

Study Arms (1)

PT-112

OTHER

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

Drug: PT-112

Interventions

PT-112 DRUG

This is a single arm study

PT-112

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously diagnosed with MM requiring treatment based on IMWG diagnostic criteria;
• 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);
• 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;
• ECOG Performance Status (PS) 0-2;
• Life expectancy \> 3 months;
• 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;
• Recovery from non-hematologic toxic effects of prior therapy to grade ≤ 1 (except alopecia) by NCI CTCAE Version 4.03;
• Adequate bone marrow (BM), renal, hepatic and metabolic function.

You may not qualify if:

• 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;
• 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);

Sponsors & Collaborators

• Promontory Therapeutics Inc.: lead

Study Sites (7)

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80220, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Oncology San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Leif Bergsagel, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-center, open-label study of PT-112 in patients with relapsed or refractory MM.

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 20, 2017
• Study Start: December 15, 2017
• Primary Completion: September 30, 2020
• Study Completion: March 1, 2021
• Last Updated: April 26, 2022

Record last verified: 2022-04

Locations

US (7)