Non-Secretory Plasma Cell MyelomaPhase 1NCT01301807
Panobinostat and Carfilzomib in Treating Participants With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing Carfilzomib and Panobinostat in people with Non-Secretory Plasma Cell Myeloma and Plasmacytosis, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/Ib trial studies the side effects and best dose of panobinostat and carfilzomib in treating participants with multiple myeloma that has come back or that isn't responding to treatment. Carfilzomib keeps cancer cells from repairing themselves. If the cancer cells cannot repair themselves, they may die. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Secretory Plasma Cell Myeloma, Plasmacytosis, Recurrent Plasma Cell Myeloma
- What is being tested?
- Carfilzomib and Panobinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jul 2011to 7 Nov 2019
- 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/refractory MM with failure to at least two lines of MM treatment which must include at least one IMiD (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) and measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio. Oligo or non secretory myeloma patients may be included, if there is measurable plasmacytosis in the bone marrow biopsy or measurable extramedullary disease.
- Male or female patients aged >/= 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Patients must meet the following laboratory criteria within 28 days of starting therapy: * Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L * Hemoglobin >/= 8 g/dl ( transfusion are permitted) * Platelet count > 70,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells or platelet count > 25,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells * aspartate aminotransferase (AST) and Alanine aminotranferease (ALT) </= 2.5 x ULN * Serum bilirubin </= 2 x ULN
- ECOG Performance Status of </= 2
- Creatinine clearance (CrCl) >/= 30 mL/minute within 28 days prior to registration, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
- Multiple Gated Acquisition (MUGA) or echocardiogram (ECHO) must demonstrate LVEF >/= 45%.
- Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Male patients, even if surgically sterilized (ie, status postvasectomy), who: Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR Agree to completely abstain from heterosexual intercourse.
Who cannot join
- Valproic acid for the treatment of cancer
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: * History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible) * Any history of ventricular fibrillation or torsade de pointes * Bradycardia defined as heart rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm. * Screening electrocardiogram (ECG) with a corrected QT interval (QTc) or QTcF > 450 msec * Right bundle branch block + left anterior hemiblock (bifascicular block) * Patients with myocardial infarction or unstable angina </= 6 months prior to starting study drug * Other clinically significant heart disease (e.g., Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
- Patients with diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
- Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
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- Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
- Patients who have received chemotherapy within </= 2 weeks by time of cycle 1 day 1 of therapy on trial ; or radiation therapy to > 30% of marrow-bearing bone within 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
- Female patients who are lactating or have a positive serum or urine pregnancy test during the Screening period.
- Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1/1b Study of the Efficacy and Safety of the Combination of Panobinostat + Carfilzomib in Patients With Relapsed/Refractory Myeloma
This phase I/Ib trial studies the side effects and best dose of panobinostat and carfilzomib in treating participants with multiple myeloma that has come back or that isn't responding to treatment. Carfilzomib keeps cancer cells from repairing themselves. If the cancer cells cannot repair themselves, they may die. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving panobinostat and carfilzomib may work better in treating participants with multiple myeloma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum recommended dose (MRD) of the combination of carfilzomib and panobinostat in patients with relapsed/refractory multiple myeloma (RRMM). (Phase I) II. To determine the overall response rate (stable disease [SD], minimal response [MR], partial response [PR], very good partial response [VGPR], near complete response/complete response [nCR/CR] of the combination. (Phase Ib)
SECONDARY OBJECTIVES:
- To determine the overall response rate (ORR), stable disease (SD), minimal response (MR), partial response (PR), very good partial response (VGPR), near complete response/complete response (nCR/CR). (Phase I) II. To determine the time to progression (TTP). (Phase I and Ib) III. To determine the progression free survival (PFS). (Phase I and Ib) IV. To determine the time to best response. (Phase I and Ib) V. To determine time to next therapy. (Phase I and Ib) VI. To determine duration of response. (Phase I and Ib) VII. To determine the overall response rate (SD, MR, PR, VGPR, nCR/CR) of the combination. (Phase Ib) VIII. To assess the safety of the combination. (Phase Ib)
OUTLINE: This is a phase I and Ib dose escalation study.
Participants receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16 and panobinostat orally (PO) once daily (QD) on days 1, 3, 5, 8, 10, and 12 of each course. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, participants may continue carfilzomib IV on days 1, 2, 15, and 16, and panobinostat PO on days 1, 3, 5, 8, 10, and 12 of each course. If the disease becomes worse, participants can receive carfilzomib on the original dosing schedule (days 1, 2, 8, 9, 15, and 16 of each course).
After completion of study treatment, participants are followed up at 30 days.
- Conditions
- Non-Secretory Plasma Cell Myeloma, Plasmacytosis, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Being tested
- Carfilzomib, Panobinostat
- 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 Kyprolis, PR-171
Given IV
PanobinostatDrug
Also called Faridak, Farydak, LBH589
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (carfilzomib, panobinostat) | Experimental | Participants receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 and panobinostat PO QD on days 1, 3, 5, 8, 10, and 12 of each course. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, participants may continue carfilzomib IV on days 1, 2, 15, and 16, and panobinostat PO on days 1, 3, 5, 8, 10, and 12 of each course. If the disease becomes worse, participants can receive carfilzomib on the original dosing schedule (days 1, 2, 8, 9, 15, and 16 of each course). Receives: Drug: Carfilzomib; Drug: Panobinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of the drug combination
Measured: At 28 days
Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: Up to 8 years
Secondary outcomes (1)
Time to progression
Will use Kaplan-Meier methods appropriate for survival analysis.
Measured: 30 days after the last dose is given
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2011 (estimated)
- Study start28 Jul 2011
- Primary completion7 Nov 2019
- Study completion7 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Secretory 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
- 63 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
- Robert Orlowski, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01301807
- Sponsor's protocol ID
- 2010-0733
- Other IDs
- NCI-2018-01845, 2010-0733, P30CA016672
- Status last verified
- Sep 2023
- First submitted
- 21 Feb 2011
- Last updated
- 29 Sep 2023
- 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 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/1b Study of the Efficacy and Safety of the Combination of Panobinostat + Carfilzomib in Patients With Relapsed/Refractory Myeloma
- ClinicalTrials.gov ID
- NCT01301807
- Acronym / sponsor ID
- 2010-0733
- Conditions
- Non-Secretory Plasma Cell Myeloma, Plasmacytosis, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 28 Jul 2011 (actual)
- Primary completion
- 7 Nov 2019 (actual)
- Study completion
- 7 Nov 2019 (actual)
- First posted
- 23 Feb 2011 (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 I/Ib trial studies the side effects and best dose of panobinostat and carfilzomib in treating participants with multiple myeloma that has come back or that isn't responding to treatment. Carfilzomib keeps cancer cells from repairing themselves. If the cancer cells cannot repair themselves, they may die. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving panobinostat and carfilzomib may work better in treating participants with multiple myeloma.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum recommended dose (MRD) of the combination of carfilzomib and panobinostat in patients with relapsed/refractory multiple myeloma (RRMM). (Phase I) II. To determine the overall response rate (stable disease [SD], minimal response [MR], partial response [PR], very good partial response [VGPR], near complete response/complete response [nCR/CR] of the combination. (Phase Ib)
SECONDARY OBJECTIVES:
- To determine the overall response rate (ORR), stable disease (SD), minimal response (MR), partial response (PR), very good partial response (VGPR), near complete response/complete response (nCR/CR). (Phase I) II. To determine the time to progression (TTP). (Phase I and Ib) III. To determine the progression free survival (PFS). (Phase I and Ib) IV. To determine the time to best response. (Phase I and Ib) V. To determine time to next therapy. (Phase I and Ib) VI. To determine duration of response. (Phase I and Ib) VII. To determine the overall response rate (SD, MR, PR, VGPR, nCR/CR) of the combination. (Phase Ib) VIII. To assess the safety of the combination. (Phase Ib)
OUTLINE: This is a phase I and Ib dose escalation study.
Participants receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16 and panobinostat orally (PO) once daily (QD) on days 1, 3, 5, 8, 10, and 12 of each course. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, participants may continue carfilzomib IV on days 1, 2, 15, and 16, and panobinostat PO on days 1, 3, 5, 8, 10, and 12 of each course. If the disease becomes worse, participants can receive carfilzomib on the original dosing schedule (days 1, 2, 8, 9, 15, and 16 of each course).
After completion of study treatment, participants are followed up at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (carfilzomib, panobinostat) | Experimental | Drug: Carfilzomib, Drug: PanobinostatParticipants receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 and panobinostat PO QD on days 1, 3, 5, 8, 10, and 12 of each course. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, participants may continue carfilzomib IV on days 1, 2, 15, and 16, and panobinostat PO on days 1, 3, 5, 8, 10, and 12 of each course. If the disease becomes worse, participants can receive carfilzomib on the original dosing schedule (days 1, 2, 8, 9, 15, and 16 of each course). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Relapsed/refractory MM with failure to at least two lines of MM treatment which must include at least one IMiD (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) and measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio. Oligo or non secretory myeloma patients may be included, if there is measurable plasmacytosis in the bone marrow biopsy or measurable extramedullary disease.
- Male or female patients aged >/= 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Patients must meet the following laboratory criteria within 28 days of starting therapy: * Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L * Hemoglobin >/= 8 g/dl ( transfusion are permitted) * Platelet count > 70,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells or platelet count > 25,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells * aspartate aminotransferase (AST) and Alanine aminotranferease (ALT) </= 2.5 x ULN * Serum bilirubin </= 2 x ULN
- ECOG Performance Status of </= 2
Key exclusion criteria (11 listed)
- Valproic acid for the treatment of cancer
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: * History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible) * Any history of ventricular fibrillation or torsade de pointes * Bradycardia defined as heart rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm. * Screening electrocardiogram (ECG) with a corrected QT interval (QTc) or QTcF > 450 msec * Right bundle branch block + left anterior hemiblock (bifascicular block) * Patients with myocardial infarction or unstable angina </= 6 months prior to starting study drug * Other clinically significant heart disease (e.g., Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
- Patients with diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
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: Kyprolis, PR-171Given IV | Drug | Treatment (carfilzomib, panobinostat) |
| PanobinostatAlso: Faridak, Farydak, LBH589Given PO | Drug | Treatment (carfilzomib, panobinostat) |
Primary outcome
Maximum tolerated dose (MTD) of the drug combination
Time frame: At 28 days
Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: Up to 8 years
1 secondary outcome
Time to progression
Time frame: 30 days after the last dose is given
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 29 Sep 2023.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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.
Robert Orlowski 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 Carfilzomib and Panobinostat in people with Non-Secretory Plasma Cell Myeloma and Plasmacytosis, 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 8 inclusion and 11 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 29 Sep 2023. 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 (MTD) of the drug combination (time frame: At 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 29 Sep 2023.