Open-label Study of TH-302 and Dexamethasone With or Without Bortezomib or Pomalidomide in Subjects With Relapsed/Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Threshold Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01522872
First received: January 6, 2012
Last updated: January 4, 2016
Last verified: May 2015
  Purpose
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.

Condition Intervention Phase
Multiple Myeloma
Drug: TH-302
Drug: TH-302 and Dexamethasone
Drug: TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib
Drug: TH-302 Dose Escalation and Dexamethasone in Combination with Pomalidomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Threshold Pharmaceuticals:

Primary Outcome Measures:
  • Number of participants with adverse events (AEs) [ Time Frame: Up to 30 days after last dose ] [ Designated as safety issue: Yes ]
  • Type of adverse events(AEs) [ Time Frame: Up to 30 days after last dose ] [ Designated as safety issue: Yes ]
  • Severity of adverse events(AEs) [ Time Frame: Up to 30 days after last dose ] [ Designated as safety issue: Yes ]
  • dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of TH-302 and dexamethasone with or without bortezomib or pomalidomide [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • recommended Phase 2 dose for TH-302 and dexamethasone with or without bortezomib or pomalidomide [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Up to 12 weeks post treatment ] [ Designated as safety issue: No ]
  • Progression-free survival(PFS) [ Time Frame: Up to 12 weeks post treatment ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) [ Time Frame: Up to 12 weeks post treatment ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 12 weeks post treatment ] [ Designated as safety issue: No ]
  • Maximum plasma concentration of TH-302 and bortezomib [ Time Frame: Cycle 1 Day 1 predose and up to 24 hours postdose ] [ Designated as safety issue: No ]

Estimated Enrollment: 98
Study Start Date: February 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy TH-302 Dose Escalation Drug: TH-302
Experimental: TH-302 and Dexamethasone Dose Expansion Drug: TH-302 and Dexamethasone
Experimental: TH-302 Dose Escalation and Dexamethasone with Bortezomib Drug: TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib
Experimental: TH-302 Dose Escalation and Dexamethasone with Pomalidomide Drug: TH-302 Dose Escalation and Dexamethasone in Combination with Pomalidomide

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 exclusion criteria are not eligible to be enrolled in this study:

  1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes.)
  2. Waldenstrom's macroglobulinemia
  3. Localized radiation therapy to only measurable disease site(s) within 2 weeks of treatment
  4. New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, or unstable arrhythmia
  5. Significant neuropathy (Grade 3 or 4, or Grade 2 with pain) at the time of enrollment or within 14 days before enrollment
  6. Symptomatic brain metastases (unless previously treated and well controlled for a period of ≥ 3 months)
  7. Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia
  8. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
  9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 14 days prior to the first dose
  10. 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
  11. Subjects who participated in an investigational drug or device study within 2 weeks prior to study entry
  12. Known or suspected active infection with HIV, hepatitis A, hepatitis B, or hepatitis C
  13. 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
  14. Females who are pregnant or breast-feeding
  15. 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
  16. Unwillingness or inability to comply with the study protocol for any reason
  17. Previous cytotoxic therapies for multiple myeloma within 3 weeks prior to study entry (2 weeks for biologic, novel therapy or corticosteroids)
  18. Subjects who have been on hormone replacement less than 2 months (subjects on hormone replacement for at least 2 months will not be excluded provided the HRT regimen remains unchanged during the conduct of the study).
  19. Prior peripheral stem cell transplant within 12 weeks of the start of study
  20. Epilepsy or other convulsive disorder requiring active management
  21. Prior therapy with a pomalidomide-containing regimen
  22. Subjects on strong inducers or strong inhibitors of cytochrome P450 CYP3A4 or CYP1A2
  23. Any other medical condition that in opinion of investigator would place patient at increased risk for toxicity during pomalidomide treatment (i.e. history of recurrent or serious thromboembolic events)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522872

Locations
United States, California
Pacific Cancer Care
Monterey, California, United States, 93940
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Maine
Maine Center for Cancer Medicine
Scarborough, Maine, United States, 04074
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Mississippi
The West Clinic
Southaven, Mississippi, United States, 38671
United States, New York
New York Oncology Hematology
Albany, New York, United States, 12208
New York Oncology Hematology
Hudson, New York, United States, 12534
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
Sponsors and Collaborators
Threshold Pharmaceuticals
  More Information

No publications provided

Responsible Party: Threshold Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01522872     History of Changes
Other Study ID Numbers: TH-CR-408 
Study First Received: January 6, 2012
Last Updated: January 4, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Threshold Pharmaceuticals:
TH-302
Relapsed/Refractory Multiple Myeloma
Bortezomib
Phase 1/2
Hypoxia
Myeloma
Evofosfamide
Pomalidomide
Pimonidazole

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Pomalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents

ClinicalTrials.gov processed this record on February 10, 2016