Recurrent Plasma Cell MyelomaPhase 1NCT02095834
Carfilzomib, Bendamustine Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing Bendamustine Hydrochloride, Carfilzomib and Dexamethasone in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase Ib trial studies the side effects and best doses of carfilzomib and bendamustine hydrochloride when given together with dexamethasone in treating patients with multiple myeloma that has returned or does not respond to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Bendamustine Hydrochloride, Carfilzomib and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2014to 7 Jan 2021
- Phase
- Phase 1
- 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
- Relapsed and or refractory multiple myeloma after at least one prior line of therapy; there is no upper limit of prior lines of therapy; patients who are ineligible for stem cell transplantation are allowed; patients should have received at least one prior novel agent (immunomodulatory agents or proteasome inhibitors); patients eligible for bone marrow transplant must have undergone bone marrow transplant (BMT) prior to enrollment
- Measurable disease, as defined by one or all of the following (assessed within 30 days prior to initiation of therapy): a) serum M-protein >= 0.5 g/d; b) urine Bence-Jones protein >= 200 mg/24 hours; c) patients with light chain only myeloma are eligible; the involved free light chain level 100 mg/L with abnormal serum free light chain ratio
- Documented relapse or progressive disease on or after any regimen (subjects refractory to the most recent regimen are eligible)
- Primary refractory patients (never responded to any therapy) are eligible
- Eastern Cooperative Oncology Group performance status 0 - 2
- Serum alanine aminotransferase (ALT) < 3.5 times the upper limit of normal within 30 days prior to cycle 1 day 1
Show all 15Show fewer
- Serum direct bilirubin < 2 mg/dL (34 Omol/L) within 30 days prior to cycle 1 day 1
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L within 30 days prior to cycle 1 day 1, without granulocyte-colony stimulating factor (G-CSF)
- Hemoglobin > 9 g/dL (80 g/L) within 30 days prior to cycle 1 day 1 (subjects may be receiving red blood cell transfusions in accordance with institutional guidelines)
- Platelet count > 100 x 10^9/L (30 x 10^9/L if myeloma involvement in the bone marrow aspirate is > 50%) within 30 days prior to cycle 1 day 1; subjects may receive platelet transfusions within institutional guidelines
- Creatinine clearance > 50 mL/minute within 30 days prior to cycle 1 day 1, either measured or calculated using a standard formula
- Patient should have a normalized or normal uric acid level prior to study entry
- Written informed consent in accordance with federal, local, and institutional guidelines
- Females of childbearing potential must have a negative pregnancy test and agree to ongoing pregnancy testing and to practice contraception; (birth control methods should be determined in consultation with the investigator)
- Male subjects must agree to practice contraception
Who cannot join
- Intolerance to previous bendamustine, carfilzomib or dexamethasone or mannitol; subjects who are allergic to bortezomib are not excluded
- Chemotherapy (approved or investigational) within 3 weeks prior to the first day of treatment or antibody therapy within 6 weeks prior to the first day of treatment
- Radiotherapy to >= 3 sites at the same time within 1 week prior to the first day of treatment
- Immunomodulatory therapy such as immunomodulatory drugs (Imids) or stem cell transplant within 28 days prior to the first day of treatment
- Pregnant or lactating females
- Major surgery within 21 days prior to the first day of treatment
Show all 19Show fewer
- Acute active infection requiring treatment (IV antibiotics, antivirals, or antifungals) within 14 days prior to the first day of treatment
- Known human immunodeficiency virus infection
- Known active hepatitis B or C infection
- Unstable angina or myocardial infarction within 4 months prior to the first day of treatment, the New York Heart Association (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 the first day of treatment
- Non-hematologic 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 the first day of treatment
- Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment
- Subjects with known or likely systemic amyloidosis
- Ongoing graft-vs-host disease
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to the first day of treatment
- 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.
About this study
Official title: A Single Center Phase Ib Study of Carfilzomib, Bendamustine, and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma
This phase Ib trial studies the side effects and best doses of carfilzomib and bendamustine hydrochloride when given together with dexamethasone in treating patients with multiple myeloma that has returned or does not respond to treatment. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as bendamustine hydrochloride, work to stop the growth of cancer cells by killing the cells. Biological therapies, such as dexamethasone, may stimulate the immune system and stop cancer cells from growing. Giving carfilzomib, bendamustine hydrochloride, and dexamethasone may be a better way to treat multiple myeloma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of carfilzomib in combination with bendamustine (bendamustine hydrochloride) and dexamethasone, up to a maximum bendamustine dose of 90 mg/m^2.
SECONDARY OBJECTIVES:
- To evaluate the safety of carfilzomib in combination with bendamustine and dexamethasone, at the MTD.
II. To evaluate the response rate and duration of response of carfilzomib in combination with bendamustine and dexamethasone, in patients with relapsed and or refractory multiple myeloma.
OUTLINE: This is a dose-escalation study of carfilzomib and bendamustine hydrochloride.
Patients receive dexamethasone orally (PO) or intravenously (IV) over 20 minutes on days 1, 2, 8, 9, 15, 16, 22, and 23 of courses 1-3; on days 1, 2, 15, and 16 of courses 4-12; and on days 1 and 2 of all subsequent courses. Patients also receive bendamustine hydrochloride IV over 10 minutes on days 1 and 2 of courses 1-3 and on day 1 of all subsequent courses and carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 of courses 1-12 and on days 1, 2, 15, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, every 3 months for 1 year, and then every 6 months thereafter.
- Being tested
- Bendamustine Hydrochloride, Carfilzomib, Dexamethasone, 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.
Bendamustine HydrochlorideDrug
Also called Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin
Given IV
CarfilzomibDrug
Also called Kyprolis, PR-171
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dexamethasone, bendamustine, carfilzomib) | Experimental | Patients receive dexamethasone PO or IV over 20 minutes on days 1, 2, 8, 9, 15, 16, 22, and 23 of courses 1-3; on days 1, 2, 15, and 16 of courses 4-12; and on days 1 and 2 of all subsequent courses. Patients also receive bendamustine hydrochloride IV over 10 minutes on days 1 and 2 of courses 1-3 and on day 1 of all subsequent courses and carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 of courses 1-12 and on days 1, 2, 15, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bendamustine Hydrochloride; Drug: Carfilzomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of carfilzomib and bendamustine hydrochloride when given together with dexamethasone, defined as the dose level below which dose limiting toxicity is observed in greater than or equal to 33% of subjects
Measured: 28 days
Recommended Phase 1b dose of carfilzomib and bendamustine hydrochloride when given together with dexamethasone
The Phase 1b recommended dose of both agents will be determined from a qualitative assessment of a broad set of considerations that include the following: safety and tolerability, disease response, and biologic activity.
Measured: Up to 6 years
Secondary outcomes (1)
Best overall response, including stringent complete remission, complete remission, very good partial remission, and partial remission
Overall response will be defined using the International Myeloma Working Group Uniform Response Criteria, with the addition of minimal response according to the European Group for Blood and Marrow Transplant criteria.
Measured: 112 days (4 courses of therapy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2014 (estimated)
- Study start24 Apr 2014
- Primary completion7 Jan 2021
- Study completion7 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Luhua (Michael) Wang, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02095834
- Sponsor's protocol ID
- 2012-0162
- Other IDs
- NCI-2014-00884, 2012-0162
- Status last verified
- Jan 2021
- First submitted
- 21 Mar 2014
- Last updated
- 11 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center Phase Ib Study of Carfilzomib, Bendamustine, and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02095834
- Acronym / sponsor ID
- 2012-0162
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 24 Apr 2014 (actual)
- Primary completion
- 7 Jan 2021 (actual)
- Study completion
- 7 Jan 2021 (actual)
- First posted
- 26 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib trial studies the side effects and best doses of carfilzomib and bendamustine hydrochloride when given together with dexamethasone in treating patients with multiple myeloma that has returned or does not respond to treatment. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as bendamustine hydrochloride, work to stop the growth of cancer cells by killing the cells. Biological therapies, such as dexamethasone, may stimulate the immune system and stop cancer cells from growing. Giving carfilzomib, bendamustine hydrochloride, and dexamethasone may be a better way to treat multiple myeloma.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of carfilzomib in combination with bendamustine (bendamustine hydrochloride) and dexamethasone, up to a maximum bendamustine dose of 90 mg/m^2.
SECONDARY OBJECTIVES:
- To evaluate the safety of carfilzomib in combination with bendamustine and dexamethasone, at the MTD.
II. To evaluate the response rate and duration of response of carfilzomib in combination with bendamustine and dexamethasone, in patients with relapsed and or refractory multiple myeloma.
OUTLINE: This is a dose-escalation study of carfilzomib and bendamustine hydrochloride.
Patients receive dexamethasone orally (PO) or intravenously (IV) over 20 minutes on days 1, 2, 8, 9, 15, 16, 22, and 23 of courses 1-3; on days 1, 2, 15, and 16 of courses 4-12; and on days 1 and 2 of all subsequent courses. Patients also receive bendamustine hydrochloride IV over 10 minutes on days 1 and 2 of courses 1-3 and on day 1 of all subsequent courses and carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 of courses 1-12 and on days 1, 2, 15, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, every 3 months for 1 year, and then every 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dexamethasone, bendamustine, carfilzomib) | Experimental | Drug: Bendamustine Hydrochloride, Drug: Carfilzomib, Drug: Dexamethasone, Other: Laboratory Biomarker AnalysisPatients receive dexamethasone PO or IV over 20 minutes on days 1, 2, 8, 9, 15, 16, 22, and 23 of courses 1-3; on days 1, 2, 15, and 16 of courses 4-12; and on days 1 and 2 of all subsequent courses. Patients also receive bendamustine hydrochloride IV over 10 minutes on days 1 and 2 of courses 1-3 and on day 1 of all subsequent courses and carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 of courses 1-12 and on days 1, 2, 15, and 16 of all subsequent courses. Courses repeat every 28 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 (15 listed)
- Relapsed and or refractory multiple myeloma after at least one prior line of therapy; there is no upper limit of prior lines of therapy; patients who are ineligible for stem cell transplantation are allowed; patients should have received at least one prior novel agent (immunomodulatory agents or proteasome inhibitors); patients eligible for bone marrow transplant must have undergone bone marrow transplant (BMT) prior to enrollment
- Measurable disease, as defined by one or all of the following (assessed within 30 days prior to initiation of therapy): a) serum M-protein >= 0.5 g/d; b) urine Bence-Jones protein >= 200 mg/24 hours; c) patients with light chain only myeloma are eligible; the involved free light chain level 100 mg/L with abnormal serum free light chain ratio
- Documented relapse or progressive disease on or after any regimen (subjects refractory to the most recent regimen are eligible)
- Primary refractory patients (never responded to any therapy) are eligible
- Eastern Cooperative Oncology Group performance status 0 - 2
Key exclusion criteria (19 listed)
- Intolerance to previous bendamustine, carfilzomib or dexamethasone or mannitol; subjects who are allergic to bortezomib are not excluded
- Chemotherapy (approved or investigational) within 3 weeks prior to the first day of treatment or antibody therapy within 6 weeks prior to the first day of treatment
- Radiotherapy to >= 3 sites at the same time within 1 week prior to the first day of treatment
- Immunomodulatory therapy such as immunomodulatory drugs (Imids) or stem cell transplant within 28 days prior to the first day of treatment
- Pregnant or lactating females
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 |
|---|---|---|
| Bendamustine HydrochlorideAlso: Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, RibomustinGiven IV | Drug | Treatment (dexamethasone, bendamustine, carfilzomib) |
| CarfilzomibAlso: Kyprolis, PR-171Given IV | Drug | Treatment (dexamethasone, bendamustine, carfilzomib) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO or IV | Drug | Treatment (dexamethasone, bendamustine, carfilzomib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (dexamethasone, bendamustine, carfilzomib) |
Primary outcome
Maximum tolerated dose of carfilzomib and bendamustine hydrochloride when given together with dexamethasone, defined as the dose level below which dose limiting toxicity is observed in greater than or equal to 33% of subjects
Time frame: 28 days
Recommended Phase 1b dose of carfilzomib and bendamustine hydrochloride when given together with dexamethasone
Time frame: Up to 6 years
The Phase 1b recommended dose of both agents will be determined from a qualitative assessment of a broad set of considerations that include the following: safety and tolerability, disease response, and biologic activity.
1 secondary outcome
Best overall response, including stringent complete remission, complete remission, very good partial remission, and partial remission
Time frame: 112 days (4 courses of therapy)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2021.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
Related trials for Recurrent Plasma Cell Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1
A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Relapsed or Refractory Multiple Myeloma
RecruitingPhase 2
Study of HBI0101 (NXC-201) CAR-T Therapy in Multiple Myeloma and Light-Chain Amyloidosis
Multiple Myeloma, Refractory to Standard Treatment, Multiple Myeloma, Relapsed
RecruitingPhase 2
Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse
Recurrent Multiple Myeloma, Refractory Multiple Myeloma
Active, not recruitingPhase 1
A Study of JNJ-87562761 in Participants With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma
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.
Luhua (Michael) Wang principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bendamustine Hydrochloride, Carfilzomib and Dexamethasone in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by M.D. Anderson Cancer Center 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 19 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 11 Jan 2021. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 of carfilzomib and bendamustine hydrochloride when given together with dexamethasone, defined as the dose level below which dose limiting toxicity is observed in greater than or equal to 33% of subjects (time frame: 28 days). 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 11 Jan 2021.