Multiple MyelomaPhase 1/2NCT02002598
Carfilzomib With Bendamustine and Dexamethasone in Multiple Myeloma
A Phase 1/2 study testing Bendamustine, Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Suzanne Lentzsch, MD at 1 site in United States.
Trial summary
This study is designed to define dose-limiting toxicity and determine preliminary evidence of efficacy of carfilzomib (CFZ) in combination with bendamustine and dexamethasone for patients with newly diagnosed multiple myeloma (MM). 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?
- Bendamustine, Carfilzomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2013to 1 Jul 2023
- 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
- Age ≥ 18 years.
- Life expectancy ≥ 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate hepatic function.
- Sufficient Absolute neutrophil count (ANC) within 14 days prior to randomization.
- Sufficient Hemoglobin within 14 days prior to randomization (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines).
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- Sufficient platelet count 14 days prior to randomization.
- Creatinine Clearance ≥ 30 mL/minute within 7 days prior to randomization.
- Left Ventricular Ejection Fraction ≥ 40%.
- Written informed consent in accordance with federal, local, and institutional guidelines.
- Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
- Male subjects must agree to practice contraception.
- Patients must have histologically or cytologically confirmed symptomatic multiple myeloma (MM). Patients should not have previously been treated.
- Prior kyphoplasty, vertebroplasty, local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture) are permitted.
- Patients are allowed up to two cycles of high dose steroids if needed for symptomatic disease before study enrollment.
Who cannot join
- Patients who have had chemotherapy for Multiple Myeloma. Exception: local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture).
- Patients currently receiving high dose systemic steroids for treatment of Multiple Myeloma in excess of 320mg total dose of dexamethasone or equivalent, patients who received an investigational agent within 5 half-lives of the agent.
- Patients with non-measurable Multiple Myeloma or primary plasma cell leukemia.
- Pregnant or lactating females.
- Major surgery within 21 days prior to enrollment.
- Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment.
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- Known human immunodeficiency virus (HIV) infection.
- Known active hepatitis B or C infection.
- Unstable angina or myocardial infarction within 4 months prior to enrollment.
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
- Uncontrolled, non-hematologic malignancy requiring active treatment.
- Patients with known brain metastases (treated or not) will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Significant neuropathy within 14 days prior to randomization.
- Known history of allergy to Captisol, or to other agents in the study.
- Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, 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 enrollment.
- 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
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Phase I/II Study of Carfilzomib in Combination With Bendamustine and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
This study is designed to define dose-limiting toxicity and determine preliminary evidence of efficacy of carfilzomib (CFZ) in combination with bendamustine and dexamethasone for patients with newly diagnosed multiple myeloma (MM).
Read the detailed description
Multiple myeloma (MM) is a malignant plasma cell disorder resulting in approximately 11,000 deaths in the United States each year. It is estimated that between 60,000-80,000 people are currently under treatment for refractory or relapsed MM. Prognosis and survival have improved over the last 20 years, but the disease is still universally fatal despite efforts to develop new and more effective chemotherapeutic regimens. Therefore, new regimens need to be developed for patients prior to peripheral blood stem cell transplant and for those unable to tolerate the toxicity of transplant.
An IRB-approved long-term retrospective chart review study (IRB-AAAU4389) was conducted to collect data for Outcome Measures relating to long-term analysis (up to 6.5 years).
- Conditions
- Multiple Myeloma
- Being tested
- Bendamustine, Carfilzomib, Dexamethasone
- Keywords
- Newly diagnosed, multiple myeloma, myeloma, bendamustine, Treanda, carfilzomib, dexamethasone, phase I, phase II, dose escalation, transplant, non-transplant, plasma cell, Kyprolis
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called Treanda
Bendamustine will be administered IV on days 1 and 2 with dose escalation up to 90 mg/m2 of each 28-day cycle.
Dose escalation is as follows:
-1 | 60 mg/m2
- | 70 mg/m2
- | 70 mg/m2
- | 90 mg/m2
- | 90mg/m2
- | 90 mg/m2
CarfilzomibDrug
Also called Kyprolis, CFZ
Carfilzomib will be administered IV on Days 1, 2, 8, 9, 15, and 16 every 28 days.
Dose Escalation is as follows:
-1 | 27 mg/m2
- | 27 mg/m2
- | 36 mg/m2
- | 36 mg/m2
- | 45 mg/m2
- | 56 mg/m2
DexamethasoneDrug
Also called Decadron, Dexamethasone Intensol, Dexpak Taperpak
Dexamethasone will be administered PO or IV, 20 mg, on 1, 2, 8, 9, 15, 16 and 22, 23 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| CFZ with bendamustine and dexamethasone | Experimental | Subjects will receive Carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days with dose escalation from 27, 36, 45 to 56 mg/ m2 . No matter what target dose the subject will receive, days 1 and 2 doses in the first cycle will always be 20 mg/m2, followed by target dose for all subsequent dates and cycles. Bendamustine will be given IV on days 1 and 2 with dose escalation up to 90 mg/m2 and dexamethasone 20 mg orally or intravenously on 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle. Study treatment will be given until 8 cycles of treatment are completed or until disease progression, whichever comes first. Receives: Drug: Bendamustine; Drug: Carfilzomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone
MTD defined as the highest dose at which ≤20% of participants experience dose-limiting toxicity (DLT), to define the recommended phase II dose. DLT were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute version 4.0. An AE was considered a DLT if it occurred in cycle 1, was deemed related to study treatment, and was one of peripheral neuropathy ≥grade 2, any non-hematologic AE ≥ grade 3, neutropenia grade 4 lasting ≥7 days or with fever, thrombocytopenia grade 4 lasting ≥7 days or with bleeding, or any AE requiring a dose reduction during cycle 1 or a delay in the start of cycle 2.
Measured: 6 months
Secondary outcomes (6)
Overall Response Rate (ORR)
ORR defined as the number of participants demonstrating complete response or partial response. Complete response defined as complete disappearance of an M-protein and no evidence of MM in the bone marrow. Partial response defined as ≥50% reduction in the level of the serum monoclonal paraprotein, reduction in 24-hour M-protein either by greater than or equal to 90% or to <200 mg, ≥50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination), no increase in the number or size of lytic bone lesions.
Measured: 2 years
Time to Next Treatment (TTNT)
The TTNT is measured from the date of initiation of treatment to the start date of the next treatment regimen.
Measured: Up to 6.5 years
Progression Free Survival (PFS)
PFS is defined as the duration of time from start of study treatment to time of progression or death, whichever occurs first.
Measured: Up to 6.5 Years
Time to Best Response
Time to the best response recorded.
Measured: 2 years
Overall Survival (OS) Rate
The percentage of people who are still alive.
Measured: Up to 6.5 Years
Number of Adverse Events (AEs)
Total number of AEs observed.
Measured: 30 Days Post Last Dose, Up to approximately 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2013 (estimated)
- Study startNov 2013
- Primary completion1 Mar 2019
- Study completion1 Jul 2023
Why it stopped: Slow accrual and loss of funding
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 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Suzanne Lentzsch, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Suzanne Lentzsch, MD, Columbia University
- Investigators
- Suzanne Lentzsch, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02002598
- Sponsor's protocol ID
- AAAJ2359
- Status last verified
- Aug 2024
- First submitted
- 2 Dec 2013
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Carfilzomib in Combination With Bendamustine and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02002598
- Acronym / sponsor ID
- AAAJ2359
- Conditions
- Multiple Myeloma
- Keywords
- Newly diagnosed, multiple myeloma, myeloma, bendamustine, Treanda, carfilzomib, dexamethasone, phase I
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual and loss of funding
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Suzanne Lentzsch, MDUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 1 Jul 2023 (actual)
- First posted
- 6 Dec 2013 (estimated)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to define dose-limiting toxicity and determine preliminary evidence of efficacy of carfilzomib (CFZ) in combination with bendamustine and dexamethasone for patients with newly diagnosed multiple myeloma (MM).
Detailed description
Multiple myeloma (MM) is a malignant plasma cell disorder resulting in approximately 11,000 deaths in the United States each year. It is estimated that between 60,000-80,000 people are currently under treatment for refractory or relapsed MM. Prognosis and survival have improved over the last 20 years, but the disease is still universally fatal despite efforts to develop new and more effective chemotherapeutic regimens. Therefore, new regimens need to be developed for patients prior to peripheral blood stem cell transplant and for those unable to tolerate the toxicity of transplant.
An IRB-approved long-term retrospective chart review study (IRB-AAAU4389) was conducted to collect data for Outcome Measures relating to long-term analysis (up to 6.5 years).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CFZ with bendamustine and dexamethasone | Experimental | Drug: Bendamustine, Drug: Carfilzomib, Drug: DexamethasoneSubjects will receive Carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days with dose escalation from 27, 36, 45 to 56 mg/ m2 . No matter what target dose the subject will receive, days 1 and 2 doses in the first cycle will always be 20 mg/m2, followed by target dose for all subsequent dates and cycles. Bendamustine will be given IV on days 1 and 2 with dose escalation up to 90 mg/m2 and dexamethasone 20 mg orally or intravenously on 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle. Study treatment will be given until 8 cycles of treatment are completed or until disease progression, whichever comes first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 years.
- Life expectancy ≥ 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate hepatic function.
- Sufficient Absolute neutrophil count (ANC) within 14 days prior to randomization.
Key exclusion criteria (17 listed)
- Patients who have had chemotherapy for Multiple Myeloma. Exception: local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture).
- Patients currently receiving high dose systemic steroids for treatment of Multiple Myeloma in excess of 320mg total dose of dexamethasone or equivalent, patients who received an investigational agent within 5 half-lives of the agent.
- Patients with non-measurable Multiple Myeloma or primary plasma cell leukemia.
- Pregnant or lactating females.
- Major surgery within 21 days prior to enrollment.
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 |
|---|---|---|
| BendamustineAlso: TreandaBendamustine will be administered IV on days 1 and 2 with dose escalation up to 90 mg/m2 of each 28-day cycle. Dose escalation is as follows: -1 | 60 mg/m2 1. | 70 mg/m2 2. | 70 mg/m2 3. | 90 mg/m2 4. | 90mg/m2 5. | 90 mg/m2 | Drug | CFZ with bendamustine and dexamethasone |
| CarfilzomibAlso: Kyprolis, CFZCarfilzomib will be administered IV on Days 1, 2, 8, 9, 15, and 16 every 28 days. Dose Escalation is as follows: -1 | 27 mg/m2 1. | 27 mg/m2 2. | 36 mg/m2 3. | 36 mg/m2 4. | 45 mg/m2 5. | 56 mg/m2 | Drug | CFZ with bendamustine and dexamethasone |
| DexamethasoneAlso: Decadron, Dexamethasone Intensol, Dexpak TaperpakDexamethasone will be administered PO or IV, 20 mg, on 1, 2, 8, 9, 15, 16 and 22, 23 of each 28-day cycle. | Drug | CFZ with bendamustine and dexamethasone |
Primary outcome
Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone
Time frame: 6 months
MTD defined as the highest dose at which ≤20% of participants experience dose-limiting toxicity (DLT), to define the recommended phase II dose. DLT were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute version 4.0. An AE was considered a DLT if it occurred in cycle 1, was deemed related to study treatment, and was one of peripheral neuropathy ≥grade 2, any non-hematologic AE ≥ grade 3, neutropenia grade 4 lasting ≥7 days or with fever, thrombocytopenia grade 4 lasting ≥7 days or with bleeding, or any AE requiring a dose reduction during cycle 1 or a delay in the start of cycle 2.
6 secondary outcomes
Overall Response Rate (ORR)
Time frame: 2 years
Time to Next Treatment (TTNT)
Time frame: Up to 6.5 years
Progression Free Survival (PFS)
Time frame: Up to 6.5 Years
Time to Best Response
Time frame: 2 years
Overall Survival (OS) Rate
Time frame: Up to 6.5 Years
Number of Adverse Events (AEs)
Time frame: 30 Days Post Last Dose, Up to approximately 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Suzanne Lentzsch, MD principal investigator
Columbia University
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 Bendamustine, Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Suzanne Lentzsch, MD 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 15 inclusion and 17 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 19 Sep 2024. 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 19 Sep 2024). 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?
Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone (time frame: 6 months). 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 19 Sep 2024.