Open-label Study of TH-302 and Dexamethasone With or Without Bortezomib or Pomalidomide in Subjects With Relapsed/Refractory Multiple Myeloma
A Phase 1/2 Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of TH-302, A Hypoxia-Activated Prodrug, and Dexamethasone With or Without Bortezomib or Pomalidomide in Subjects With Relapsed/Refractory Multiple Myeloma
1 other identifier
interventional
98
1 country
10
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 multiple-myeloma
Started Feb 2012
Typical duration for phase_1 multiple-myeloma
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 6, 2012
CompletedFirst Posted
Study publicly available on registry
February 1, 2012
CompletedStudy Start
First participant enrolled
February 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2017
CompletedJune 2, 2016
June 1, 2016
4.6 years
January 6, 2012
June 1, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
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
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
Secondary Outcomes (5)
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
Study Arms (4)
Monotherapy TH-302 Dose Escalation
EXPERIMENTALTH-302 and Dexamethasone Dose Expansion
EXPERIMENTALTH-302 Dose Escalation and Dexamethasone with Bortezomib
EXPERIMENTALTH-302 Dose Escalation and Dexamethasone with Pomalidomide
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- At least 18 years of age.
- 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.
- Relapsed/refractory multiple myeloma for which no standard therapy options are anticipated to result in a durable remission.
- Receipt of at least two prior therapies as indicated by protocol
- Subjects with measurable disease
- ECOG performance status of less than or equal to 2
- Acceptable liver function
- Acceptable renal function
- Acceptable hematologic status
- 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.
- 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.
You may not qualify if:
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes.)
- Waldenstrom's macroglobulinemia
- Localized radiation therapy to only measurable disease site(s) within 2 weeks of treatment
- New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, or unstable arrhythmia
- Significant neuropathy (Grade 3 or 4, or Grade 2 with pain) at the time of enrollment or within 14 days before enrollment
- Symptomatic brain metastases (unless previously treated and well controlled for a period of ≥ 3 months)
- Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 14 days prior to the first dose
- Previously treated malignancies, except for adequately treated non-melanoma skin cancer (basal cell or squamous cell), in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
- Subjects who participated in an investigational drug or device study within 2 weeks prior to study entry
- Known or suspected active infection with HIV, hepatitis A, hepatitis B, or hepatitis C
- Subjects who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation similar to TH-302, bortezomib (for subjects enrolled in Part C only), pomalidomide (Part D), dexamethasone or pimonidazole
- Females who are pregnant or breast-feeding
- Concomitant psychiatric disease or medical condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Pacific Cancer Care
Monterey, California, 93940, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Maine Center for Cancer Medicine
Scarborough, Maine, 04074, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
The West Clinic
Southaven, Mississippi, 38671, United States
New York Oncology Hematology
Albany, New York, 12208, United States
New York Oncology Hematology
Hudson, New York, 12534, United States
The West Clinic
Memphis, Tennessee, 38120, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 6, 2012
First Posted
February 1, 2012
Study Start
February 1, 2012
Primary Completion
September 1, 2016
Study Completion
September 1, 2017
Last Updated
June 2, 2016
Record last verified: 2016-06