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Multiple MyelomaPhase 1/2NCT01522872

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 study testing TH-302, TH-302 and Dexamethasone and TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib in people with Multiple Myeloma, run by Threshold Pharmaceuticals at 10 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
TH-302, TH-302 and Dexamethasone and TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
10 sitesUnited States
Study dates
Feb 2012to Sep 2017
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • Subjects who meet any of the following exclusion criteria are not eligible to be enrolled in this study:
  • 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
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  • 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
  • Unwillingness or inability to comply with the study protocol for any reason
  • Previous cytotoxic therapies for multiple myeloma within 3 weeks prior to study entry (2 weeks for biologic, novel therapy or corticosteroids)
  • 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).
  • Prior peripheral stem cell transplant within 12 weeks of the start of study
  • Epilepsy or other convulsive disorder requiring active management
  • Prior therapy with a pomalidomide-containing regimen
  • Subjects on strong inducers or strong inhibitors of cytochrome P450 CYP3A4 or CYP1A2
  • 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)

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • New York Oncology Hematology

    Albany, New York, 12208

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • New York Oncology Hematology

    Hudson, New York, 12534

  • The West Clinic

    Memphis, Tennessee, 38120

  • Pacific Cancer Care

    Monterey, California, 93940

  • Maine Center for Cancer Medicine

    Scarborough, Maine, 04074

  • The West Clinic

    Southaven, Mississippi, 38671

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
TH-302, TH-302 and Dexamethasone, TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib, TH-302 Dose Escalation and Dexamethasone in Combination with Pomalidomide
Keywords
TH-302, Relapsed/Refractory Multiple Myeloma, Bortezomib, Phase 1/2, Hypoxia, Myeloma, Evofosfamide, Pomalidomide, Pimonidazole
Medical subject headings
Multiple Myeloma, Hypoxia, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TH-302Drug

  • TH-302 and DexamethasoneDrug

  • TH-302 Dose Escalation and Dexamethasone in Combination with BortezomibDrug

  • TH-302 Dose Escalation and Dexamethasone in Combination with PomalidomideDrug

Study groups in NCT01522872
Study groupRoleWhat they receive
Monotherapy TH-302 Dose EscalationExperimentalNot described
Receives: Drug: TH-302
TH-302 and Dexamethasone Dose ExpansionExperimentalNot described
Receives: Drug: TH-302 and Dexamethasone
TH-302 Dose Escalation and Dexamethasone with BortezomibExperimentalNot described
Receives: Drug: TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib
TH-302 Dose Escalation and Dexamethasone with PomalidomideExperimentalNot described
Receives: Drug: TH-302 Dose Escalation and Dexamethasone in Combination with Pomalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with adverse events (AEs)

    Measured: Up to 30 days after last dose

  2. Type of adverse events(AEs)

    Measured: Up to 30 days after last dose

  3. Severity of adverse events(AEs)

    Measured: Up to 30 days after last dose

  4. dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of TH-302 and dexamethasone with or without bortezomib or pomalidomide

    Measured: 2 years

  5. recommended Phase 2 dose for TH-302 and dexamethasone with or without bortezomib or pomalidomide

    Measured: 2 years

Secondary outcomes (5)

  1. Overall Survival (OS)

    Measured: Up to 12 weeks post treatment

  2. Progression-free survival(PFS)

    Measured: Up to 12 weeks post treatment

  3. Duration of Response (DOR)

    Measured: Up to 12 weeks post treatment

  4. 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

    Measured: Up to 12 weeks post treatment

  5. Maximum plasma concentration of TH-302 and bortezomib

    Measured: Cycle 1 Day 1 predose and up to 24 hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionSep 2016 (estimated)
  4. Study completionSep 2017 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01522872
Sponsor's protocol ID
TH-CR-408
Status last verified
Jun 2016
First submitted
6 Jan 2012
Last updated
2 Jun 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TH-302, TH-302 and Dexamethasone and TH-302 Dose Escalation and Dexamethasone in Combination with Bortezomib in people with Multiple Myeloma, run by Threshold Pharmaceuticals at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with adverse events (AEs) (time frame: Up to 30 days after last dose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01522872.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2016.

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