Refractory Multiple MyelomaPhase 1/2NCT00719901
Obatoclax and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing obatoclax mesylate, bortezomib and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I/II trial is studying the side effects and best dose of obatoclax when given together with bortezomib and to see how well they work in treating patients with relapsed or refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma
- What is being tested?
- obatoclax mesylate, bortezomib and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Jun 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Symptomatic multiple myeloma, meeting the following criteria at original diagnosis:
- Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
- Symptomatic disease (e.g.,anemia, hypercalcemia, bone disease, or renal dysfunction) that requires the initiation of therapy
- Measurable diseases assessed by one of the following:
- Monoclonal plasma cells detectable in the bone marrow
- Monoclonal serum spike detectable by serum protein electrophoresis or immunofixation
Show all 42Show fewer
- Monoclonal protein detectable in the urine by electrophoresis or immunofixation
- Abnormal levels of the serum free light chains with an abnormal ratio between kappa and lambda
- Progressive disease after ≥ 1 prior therapy for myeloma
- Previously treated with ≤ 10 courses (30 weeks) of bortezomib and had no disease progression during therapy OR completed bortezomib therapy within the past 6 weeks
- No prior discontinuation of bortezomib therapy due to drug intolerance
- No known brain metastases
- No intracranial edema, intracranial metastasis, or active epidural disease
- Patients with lytic lesions of the cranium secondary to myeloma are eligible
- ECOG performance status 0-2
- Life expectancy > 6 months
- ANC ≥ 1,000/mm³
- Platelet count ≥ 50,000/mm³
- Bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Creatinine ≤ 2 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No peripheral neuropathy > NCI toxicity grade 2
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to obatoclax mesylate or bortezomib
- No concurrent uncontrolled illness including, but not limited to the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia, including QTc > 450 msec
- Psychiatric illness/social situations that would limit compliance with study requirements
- No history of seizure disorder
- No other neurological disorder or dysfunction that, in the opinion of the investigator, would confound the evaluation of neurologic and other adverse events associated with obatoclax mesylate
- At least 14 days since prior chemotherapy and recovered
- More than 28 days since prior experimental drugs and/or investigational agents
- No concurrent CYP interactive medications
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
- Growth factors and bisphosphonates are allowed as medically indicated
- Prednisone (≤ 10 mg per day) allowed provided there has been no dose increase within the past 2 weeks
- No other concurrent investigational agents
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
This phase I/II trial is studying the side effects and best dose of obatoclax when given together with bortezomib and to see how well they work in treating patients with relapsed or refractory multiple myeloma. Obatoclax and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obatoclax together with bortezomib may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose and recommended phase II dose of obatoclax mesylate when given in combination with bortezomib in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the response rate (complete response, partial response, and very good partial response) in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
- To determine the duration of progression-free and overall survival of these patients.
II. To evaluate the incidence of toxicities of this regimen in these patients. III. To explore the utility of genetic markers based on initial evidence that they are predictive of drug responsiveness and/or successful target inhibition.
OUTLINE: This is a multicenter, phase I, dose-escalation study of obatoclax mesylate followed by a phase II study.
Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.
- Conditions
- Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
- Being tested
- obatoclax mesylate, bortezomib, laboratory biomarker analysis
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
obatoclax mesylateDrug
Also called GX15-070MS
Given IV
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: obatoclax mesylate; Drug: bortezomib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)
DLT was defined as any events that is determined to be possibly, probably, or definitely related to the combination of bortezomib and GX15-070 (as determined by the investigator) and occurring during the first cycle of treatment, irrespective of whether the toxicity resolved. Hematologic DLT measures were assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading.
Measured: Up to 21 days of every first course
Proportion of Patients Who Achieve a Partial Response or Better. (Phase II)
In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.
Measured: From baseline to up to 3 years
Secondary outcomes (5)
Number of Patients Who Have at Least a Partial Response (Phase I)
In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.
Measured: From baseline to up to 3 years
Time to Progression (Phase II)
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to the time of progression
Overall Survival (Phase II)
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to death due to any cause
Time to Treatment Failure (Phase II)
Time to treatment failure will be evaluated using the method of Kaplan-Meier.
Measured: Time from study entry to the date patients end treatment
Toxicity as Assessed by the National Cancer Institute (NCI) CTCAE v 3.0 (Phase II)
Toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all toxicities data that is graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and toxicities will be evaluated using all patients who have received any study treatment.
Measured: From baseline to up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionApr 2011
- Study completionJun 2012
Why it stopped: This trial was terminated due to slow accrual and the drug supply of Obatoclax during the phase I; therefore, the phase II portion will never open.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Refractory Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alexander Stewart, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00719901
- Sponsor's protocol ID
- NCI-2009-00255
- Other IDs
- NCI-2009-00255, CDR0000597950, MAYO-MC068A, MC068A, 7952, N01CM62205, P01CA136447, N01CM62208
- Status last verified
- Oct 2013
- First submitted
- 19 Jul 2008
- Last updated
- 12 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Obatoclax Mesylate (GX15-070MS) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00719901
- Acronym / sponsor ID
- NCI-2009-00255
- Conditions
- Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This trial was terminated due to slow accrual and the drug supply of Obatoclax during the phase I; therefore, the phase II portion will never open.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 22 Jul 2008 (estimated)
- Results
- Posted 9 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial is studying the side effects and best dose of obatoclax when given together with bortezomib and to see how well they work in treating patients with relapsed or refractory multiple myeloma. Obatoclax and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obatoclax together with bortezomib may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose and recommended phase II dose of obatoclax mesylate when given in combination with bortezomib in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the response rate (complete response, partial response, and very good partial response) in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
- To determine the duration of progression-free and overall survival of these patients.
II. To evaluate the incidence of toxicities of this regimen in these patients. III. To explore the utility of genetic markers based on initial evidence that they are predictive of drug responsiveness and/or successful target inhibition.
OUTLINE: This is a multicenter, phase I, dose-escalation study of obatoclax mesylate followed by a phase II study.
Patients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: obatoclax mesylate, Drug: bortezomib, Other: laboratory biomarker analysisPatients receive obatoclax mesylate IV over 3 hours and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- Symptomatic multiple myeloma, meeting the following criteria at original diagnosis:
- Measurable diseases assessed by one of the following:
- Progressive disease after ≥ 1 prior therapy for myeloma
- Previously treated with ≤ 10 courses (30 weeks) of bortezomib and had no disease progression during therapy OR completed bortezomib therapy within the past 6 weeks
- No known brain metastases
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| obatoclax mesylateAlso: GX15-070MSGiven IV | Drug | Treatment (enzyme inhibitor therapy) |
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Treatment (enzyme inhibitor therapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (enzyme inhibitor therapy) |
Primary outcome
Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)
Time frame: Up to 21 days of every first course
DLT was defined as any events that is determined to be possibly, probably, or definitely related to the combination of bortezomib and GX15-070 (as determined by the investigator) and occurring during the first cycle of treatment, irrespective of whether the toxicity resolved. Hematologic DLT measures were assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading.
Proportion of Patients Who Achieve a Partial Response or Better. (Phase II)
Time frame: From baseline to up to 3 years
In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.
5 secondary outcomes
Number of Patients Who Have at Least a Partial Response (Phase I)
Time frame: From baseline to up to 3 years
Time to Progression (Phase II)
Time frame: Time from registration to the time of progression
Overall Survival (Phase II)
Time frame: Time from registration to death due to any cause
Time to Treatment Failure (Phase II)
Time frame: Time from study entry to the date patients end treatment
Toxicity as Assessed by the National Cancer Institute (NCI) CTCAE v 3.0 (Phase II)
Time frame: From baseline to up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Stewart principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing obatoclax mesylate, bortezomib and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site 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 42 inclusion and 0 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: stopped early, as of the sponsor's last update on 12 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 9 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Dose-limiting Toxicity (DLT) Incidents (Phase I) (time frame: Up to 21 days of every first course). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jan 2015.