Multiple Myeloma
Conditions
Keywords
TH-302, Relapsed/Refractory Multiple Myeloma, Bortezomib, Phase 1/2, Hypoxia, Myeloma, Evofosfamide, Pomalidomide, Pimonidazole
Brief summary
This phase 2 study is designed to evaluate the safety and tolerability activity of TH-302 and dexamethasone with or without bortezomib or pomalidomide in subjects with relapsed/refractory multiple myeloma.
Detailed description
This is the initial study of TH-302 in subjects with relapsed/refractory multiple myeloma. It is an open-label dose-escalation study to determine the DLTs, MTD, safety and preliminary efficacy of TH-302 and dexamethasone with a Simon two-stage expansion at the MTD. The study will also investigate the DLTs, MTD, safety and preliminary efficacy of TH-302, dexamethasone and bortezomib; and the DLTs, MTD, safety and preliminary efficacy of TH-302, dexamethasone and pomalidomide. As such, the study is separated into four parts. Treatment will be administered until disease progression or unacceptable toxicity, or 12 cycles (Arm A, Arm B and Arm C) or 9 cycles (Arm D) have been completed.
Interventions
DRUGTH-302
DRUGTH-302 and Dexamethasone
DRUGTH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib
DRUGTH-302 Dose Escalation and Dexamethasone in Combination with Pomalidomide
Sponsors
Threshold Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age. 2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee. 3. Relapsed/refractory multiple myeloma for which no standard therapy options are anticipated to result in a durable remission. 4. Receipt of at least two prior therapies as indicated by protocol 5. Subjects with measurable disease 6. ECOG performance status of less than or equal to 2 7. Acceptable liver function 8. Acceptable renal function 9. Acceptable hematologic status 10. For Part A, B, C subjects: Women of childbearing potential must have a negative serum pregnancy test and women and men subjects must agree to use effective means of contraception with their partner as indicated by protocol For Part D subjects: a negative serum pregnancy test is required within 10- 14 days prior to initiating with pomalidomide, AND a negative serum pregnancy test within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control at least 28 days before she starts taking pomalidomide. Women of childbearing potential must enroll into and follow all requirements of the POMALYST REMS program, which includes adhering to the scheduled pregnancy testing. Men must agree to use a latex or synthetic condom during sexual contact with women of child bearing potential even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure, or when a female patient misses her period or if there is any abnormality in her menstrual bleeding. 11. Subjects must adhere to the study visit schedule and other protocol requirements and receive outpatient therapy and laboratory monitoring at the institute that administers the study drug.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Severity of adverse events(AEs) | Up to 30 days after last dose |
| dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of TH-302 and dexamethasone with or without bortezomib or pomalidomide | 2 years |
| recommended Phase 2 dose for TH-302 and dexamethasone with or without bortezomib or pomalidomide | 2 years |
| Number of participants with adverse events (AEs) | Up to 30 days after last dose |
| Type of adverse events(AEs) | Up to 30 days after last dose |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Up to 12 weeks post treatment |
| Progression-free survival(PFS) | Up to 12 weeks post treatment |
| Duration of Response (DOR) | Up to 12 weeks post treatment |
| relationship between hypoxia within the bone marrow of subjects with relapsed/refractory multiple myeloma and response to TH-302 and dexamethasone with or without bortezomib or pomalidomide using markers of hypoxia | Up to 12 weeks post treatment |
| Maximum plasma concentration of TH-302 and bortezomib | Cycle 1 Day 1 predose and up to 24 hours postdose |
Countries
United States
Outcome results
None listed