Relapse Multiple MyelomaPhase 2NCT01775553
Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib
A Phase 2 study testing Carfilzomib in people with Relapse Multiple Myeloma and Refractory Multiple Myeloma, run by Ajai Chari at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety and activity of the investigational drug known as carfilzomib in the treatment of multiple myeloma (MM) when it is given at doses above the usual dose after the standard dosing has become ineffective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapse Multiple Myeloma, Refractory Multiple Myeloma
- What is being tested?
- Carfilzomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to May 2016
- Phase
- Phase 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
- Disease-related:
- Multiple myeloma
- Subjects must have measurable disease, defined as one or both of the following:
- Serum M-protein ≥ 1.0 g/dL
- Urine M-protein ≥ 200 mg/24 hours
- Free light chains: Only in patients without measureable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels must be at least 10 mg/dl.
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- Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
- Subjects must have progressed on standard dose 20/27 mg/m2 and schedule of carfilzomib without having had any carfilzomib related grade 3 or 4 toxicities.
- Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen
- Subjects must have received prior treatment with bortezomib, and either thalidomide or lenalidomide
- Subjects must have received an alkylating agent unless contraindicated. Subjects may have received these agents alone or in combination with other myeloma treatments.
- Demographic:
- Age ≥ 18 years
- Life expectancy ≥ 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Laboratory/Radiology
- Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to randomization
- Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
- Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to randomization independent of G-CSF for ≥ 1 week and pegylated G-CSF for ≥ 2 weeks
- Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines)
- Screening platelet count ≥ 50 × 109/L independent of platelet transfusions for at least 2 weeks
- Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to randomization, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
- LVEF ≥ 40% within 30 days before Cycle 1 Day 1. 2-D Transthoracic Echocardiogram (ECHO) is the preferred method of evaluation; MUGA is acceptable if ECHO is not available.
Who cannot join
- Disease-related
- Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within the last three weeks
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose (unless enrolling on this study after progression CMAP compassionate use carfilzomib protocol, in which case subject may proceed with current study treatment on next expected date of treatment)
- Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
- Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose, whichever time is greater (unless enrolling after progression on CMAP compassionate use carfilzomib protocol)
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- Concurrent Conditions
- Pregnant or lactating females
- Major surgery within 21 days prior to randomization
- Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
- Known human immunodeficiency virus infection
- Known active hepatitis B or C infection
- Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
- Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
- Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
- Contraindication to any of the required concomitant drugs or supportive treatments, including antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization
- Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Recapturing Disease Response: A Phase II Study of High Dose Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma Who Have Progressed on Standard Dose Carfilzomib
The purpose of this study is to determine the safety and activity of the investigational drug known as carfilzomib in the treatment of multiple myeloma (MM) when it is given at doses above the usual dose after the standard dosing has become ineffective. The other purpose of this study is to understand what causes the multiple myeloma to become resistant to carfilzomib and whether this can be overcome in the laboratory.
Read the detailed description
This is an open label, single center, phase II study of high dose carfilzomib. Patients with relapsed or relapsed/refractory myeloma and with progression of disease on standard dosing (20/27 mg/m2) and schedule of carfilzomib will be initially treated at dose level 1, carfilzomib 20/56 mg/m2. During Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. If a minimal response or better is achieved (and therefore disease response is recaptured) a bone marrow biopsy will be repeated.
If 56 mg/m2 is not tolerated, the dose of carfilzomib will be reduced to dose level -1 i.e. 45 mg/m2. If a subject does not tolerate 45 mg/m2 then the dose would be further reduced to dose level -2 i.e. 36 mg/m2. If the subject does not tolerate 36 mg/m2, then this subject would have to come off study.
Dexamethasone 8 mg po/IV will be administered prior to all carfilzomib doses.
Once a patient develops disease progression on this study, the patient may return to receiving the maximum tolerated dose of carfilzomib by that patient with the addition of a therapeutic dosing of dexamethasone (a total of 20-40 mg weekly). An IMId (e.g. thalidomide or lenalidomide) and/or an alkylator can also be added to carfilzomib 27 or 36 mg/m2 per investigator discretion either concurrent with the addition of dexamethasone or subsequent to disease progression on carfilzomib with concurrent therapeutic dexamethasone.
- Being tested
- Carfilzomib
- Keywords
- Relapsed Multiple Myeloma, Refractory Multiple Myeloma, High-Dose Carfilzomib, Standard Dose Carfilzomib, Carfilzomib
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called High Dose Carfilzomib
During Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. Each cycle is 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib | Experimental | All patients will receive Carfilzomib Receives: Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Efficacy of High Dose Carfilzomib
The safety and efficacy of high dose carfilzomib who developed disease progression on the standard dosing and schedule of carfilzomib as measured by number of participants with adverse events
Measured: up to 4 years
Secondary outcomes (4)
Progression Free Survival (PFS)
Measured: up to 4 years
Overall Response Rate (ORR)
Overall Response Rate defined in categories
Measured: up to 4 years
Duration of Response to High Dose Carfilzomib
Measured: up to 4 years
Markers of ER Stress
The markers of ER stress signaling (both apoptotic and prosurvival) in MM cells from patients in this study and to determine if the balance of apoptotic versus prosurvival signaling changes upon recapture of response with carfilzomib dose escalation relative to the time of study entry.
Measured: up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2013 (estimated)
- Study startSep 2013
- Primary completionMay 2016
- Study completionMay 2016
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 Relapse Multiple MyelomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ajai Chari
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Ajai Chari, Icahn School of Medicine at Mount Sinai
- Investigators
- Ajai Chari, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01775553
- Sponsor's protocol ID
- GCO 12-1506
- Other IDs
- CAR IST 534
- Status last verified
- May 2017
- First submitted
- 25 Sep 2012
- Last updated
- 21 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recapturing Disease Response: A Phase II Study of High Dose Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma Who Have Progressed on Standard Dose Carfilzomib
- ClinicalTrials.gov ID
- NCT01775553
- Acronym / sponsor ID
- GCO 12-1506
- Keywords
- Relapsed Multiple Myeloma, Refractory Multiple Myeloma, High-Dose Carfilzomib, Standard Dose Carfilzomib, Carfilzomib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Ajai ChariUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Sep 2013
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 25 Jan 2013 (estimated)
- Results
- Posted 21 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and activity of the investigational drug known as carfilzomib in the treatment of multiple myeloma (MM) when it is given at doses above the usual dose after the standard dosing has become ineffective. The other purpose of this study is to understand what causes the multiple myeloma to become resistant to carfilzomib and whether this can be overcome in the laboratory.
Detailed description
This is an open label, single center, phase II study of high dose carfilzomib. Patients with relapsed or relapsed/refractory myeloma and with progression of disease on standard dosing (20/27 mg/m2) and schedule of carfilzomib will be initially treated at dose level 1, carfilzomib 20/56 mg/m2. During Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. If a minimal response or better is achieved (and therefore disease response is recaptured) a bone marrow biopsy will be repeated.
If 56 mg/m2 is not tolerated, the dose of carfilzomib will be reduced to dose level -1 i.e. 45 mg/m2. If a subject does not tolerate 45 mg/m2 then the dose would be further reduced to dose level -2 i.e. 36 mg/m2. If the subject does not tolerate 36 mg/m2, then this subject would have to come off study.
Dexamethasone 8 mg po/IV will be administered prior to all carfilzomib doses.
Once a patient develops disease progression on this study, the patient may return to receiving the maximum tolerated dose of carfilzomib by that patient with the addition of a therapeutic dosing of dexamethasone (a total of 20-40 mg weekly). An IMId (e.g. thalidomide or lenalidomide) and/or an alkylator can also be added to carfilzomib 27 or 36 mg/m2 per investigator discretion either concurrent with the addition of dexamethasone or subsequent to disease progression on carfilzomib with concurrent therapeutic dexamethasone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib | Experimental | Drug: CarfilzomibAll patients will receive Carfilzomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Multiple myeloma
- Subjects must have measurable disease, defined as one or both of the following:
- Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
- Subjects must have progressed on standard dose 20/27 mg/m2 and schedule of carfilzomib without having had any carfilzomib related grade 3 or 4 toxicities.
- Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen
Key exclusion criteria (20 listed)
- Disease-related
- Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within the last three weeks
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose (unless enrolling on this study after progression CMAP compassionate use carfilzomib protocol, in which case subject may proceed with current study treatment on next expected date of treatment)
- Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
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 |
|---|---|---|
| CarfilzomibAlso: High Dose CarfilzomibDuring Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. Each cycle is 28 days. | Drug | Carfilzomib |
Primary outcome
Safety and Efficacy of High Dose Carfilzomib
Time frame: up to 4 years
The safety and efficacy of high dose carfilzomib who developed disease progression on the standard dosing and schedule of carfilzomib as measured by number of participants with adverse events
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: up to 4 years
Overall Response Rate (ORR)
Time frame: up to 4 years
Duration of Response to High Dose Carfilzomib
Time frame: up to 4 years
Markers of ER Stress
Time frame: up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Relapse Multiple Myeloma
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A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1/2
A Trial to Study if REGN17372 in Combination With Linvoseltamab is Tolerable for Adult Participants With Relapsed/Refractory Multiple Myeloma
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A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments
Multiple Myeloma
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
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.
Ajai Chari, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib in people with Relapse Multiple Myeloma and Refractory Multiple Myeloma, run by Ajai Chari 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 23 inclusion and 20 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: finished, as of the sponsor's last update on 21 Jun 2017. 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 phase mean?
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 21 Jun 2017). 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?
Safety and Efficacy of High Dose Carfilzomib (time frame: up to 4 years). 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 21 Jun 2017.