Non-Hodgkin LymphomaPhase 1NCT02142530
Carfilzomib Plus Belinostat in Relapsed/Refractory NHL
A Phase 1 study testing Carfilzomib and Belinostat in people with Non-Hodgkin Lymphoma and Diffuse Large B-cell Lymphoma, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This research study is evaluating a drug called carfilzomib used in combination with another drug called belinostat with participants who have relapsed or refractory non-Hodgkin lymphoma (NHL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- Carfilzomib and Belinostat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2014to Jan 2018
- 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
- Subjects must have histologically confirmed relapsed or refractory non-Hodgkin lymphoma that is not a candidate for standard curative therapy. NHL subtypes include: Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma, Marginal zone lymphoma, Lymphoplasmacytic lymphoma, Peripheral T-cell lymphomas, and Follicular lymphoma of any grade.
- Patients must have received at least one prior systemic therapy for lymphoma. A washout period of at least 3 weeks is required from the most recent prior therapy.
- Age ≥18 years
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A)
- Participants must have organ and marrow function as defined below:
- absolute neutrophil count ≥1,000/mcL
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- platelets ≥75,000/mcL
- total bilirubin ≤ 2 × institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) ≤ 3 × institutional upper limit of normal
- creatinine ≤1.5 × institutional upper limit of normal
- --- OR
- creatinine clearance ≥45 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Participants may have either measurable or non-measurable disease, but in all cases eligible patients must have disease that can be clinically evaluated for improvement or progression.
- Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual grade 1 toxicity, e.g., grade 1 peripheral neuropathy, and residual alopecia are allowed).
- The effects of carfilzomib and belinostat on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Participants who have had chemotherapy or radiotherapy within 3 weeks (8 weeks for radioimmunotherapy) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
- Participants who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib or belinostat
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
- Pregnant or lactating patients.
- Prior history of another malignancy (except for non-melanoma skin cancer, in situ cervical or breast cancer, or prostate cancer detectable only by PSA) unless disease free for over one year
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- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Congestive heart failure of any severity (NYHA class I-IV)
- Any active angina or any unstable angina pectoris or myocardial infarction within one year of study entry.
- Left ventricular ejection fraction below the lower limit of normal
- Greater than grade 1 peripheral neuropathy at baseline
- Congenital long QT syndrome or history of torsades de pointes
- Baseline QTc interval > 500 msec
- Concomitant medications required on dosing days that increase risk of torsades de pointes
- Subjects with known HIV infection
- Active hepatitis B or C infection
- 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 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 randomization
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth-Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Carfilzomib Plus Belinostat in Relapsed/Refractory Non-Hodgkin Lymphoma Subtypes: A Phase 1 Study
This research study is evaluating a drug called carfilzomib used in combination with another drug called belinostat with participants who have relapsed or refractory non-Hodgkin lymphoma (NHL).
Read the detailed description
The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have NHL, not everyone who participates in this research study will receive the same dose of the study drug. The dose the each participant gets will depend on the number of participants who have been enrolled in the study prior and how the dose was tolerated.
- Study Drug(s): Both carfilzomib and belinostat will be given through a vein in the participant's arm (IV infusion). Each treatment cycle lasts 28 days (4 weeks).
- Carfilzomib will be given on Days 1-2, 8-9, and 15-16 of each cycle. The carfilzomib infusion will be given over about 10 minutes during the first cycle. However if the dose is increased over the course of the trial, or if in one of the groups that joins the study at a higher dose level, the infusion will last about 30 minutes. All participants will remain at the clinic under observation for at least 1 hour following each dose of carfilzomib during Cycle 1 and after the Cycle 2 Day 1 dose.
- Belinostat will be given on Days 1-5 of each cycle. The belinostat infusion will be given over about 30 minutes.
- Clinical Exams: During all cycles the participant will have a physical exam and will be asked questions about their general health and specific questions about any problems any medications you may be taking.
- Pharmacokinetic (PK) blood tests: One of the main reasons for this study is to find the highest dose of the study drug combination that can be used safely without experiencing severe side effects to use for future studies. Once this dose is found (the maximum tolerated dose, or MTD), additional blood samples will be drawn from a small set of participants (about 5 participants total) to learn more about the activity of the study drugs in the body over a period of time, including the ways the study drugs are absorbed, distributed, and then released from the body. If participating in this group (the participant will be informed from the Investigator) these pharmacokinetic (PK) samples will be drawn repeatedly over a period of 24 hours on certain days: Blood samples will be drawn at 0, 15, 30, 60, 90 minutes, and 2, 4, 6, 8 and 24 hours after the study drug dosing on Days 1-2, 4-5, and 9 of Cycle 1.
- Scans (or Imaging tests): Tumor assessment by CT or PET CT scans once every 8 weeks (every other cycle).
- Conditions
- Non-Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Peripheral T-cell Lymphoma
- Being tested
- Carfilzomib, Belinostat
- Keywords
- NHL, DLBCL, PTCL, Marginal zone lymphoma, lymphoplasmacytic lymphoma, Waldenstrom's macroglobulinemia
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, T-Cell, Peripheral, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis®
BelinostatDrug
Also called Beleodaq
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib/ Belinostat | Experimental | Carfilzomib and Belinostat will be administered on a 28-day schedule.
* Carfilzomib will be given on days 1-2, 8-9, and 15-16 of each cycle, beginning at a dose of 20 mg/m2 (dose level 0).
* Belinostat will be given on days 1-5 beginning at a dose of 600 mg/m2.
* Belinostat dosing will precede carfilzomib dosing on days when both drugs are administered. In dose level 1 and beyond, carfilzomib will be given at a dose of 20mg/m2 with cycle 1, and then escalated with cycle 2
* A maximum of four dose levels are planned with carfilzomib escalated no higher than 20/36 mg/m2 and belinostat escalated no higher than 900 mg/m2. Receives: Drug: Carfilzomib; Drug: Belinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated doses of carfilzomib and belinostat in combination
Measured: Baseline, 28 days
Secondary outcomes (3)
Number of Participants with Serious Adverse Events
Measured: 28 days
Plasma Concentration Time Profiles
Limited PK assessment to characterize the plasma concentration time profiles at times when the two compounds are given together and alone during the first cycle of therapy in a group of 5 patients treated with the MTD of the combination
Measured: 0, 5, 15, 30, 60, 90 min and 2, 4, 6, 8, and 24 hours
Objective response rate
Preliminary assessment of efficacy of carfilzomib and belinostat based on objective response rate For the purposes of this study, participants with measurable disease should be re-evaluated every 8 weeks. Participants with low-grade histologies will be staged and re-staged with CT scans of the chest, abdomen, and pelvis. Participants with high-grade histologies will be staged and re-staged with PET/CT scans.
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startOct 2014
- Primary completionMar 2017
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Principal investigator, Jeremy Abramson, MD, Massachusetts General Hospital
- Investigators
- Jeremy Abramson, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02142530
- Sponsor's protocol ID
- 14-096
- Status last verified
- Jan 2018
- First submitted
- 16 May 2014
- Last updated
- 25 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carfilzomib Plus Belinostat in Relapsed/Refractory Non-Hodgkin Lymphoma Subtypes: A Phase 1 Study
- ClinicalTrials.gov ID
- NCT02142530
- Acronym / sponsor ID
- 14-096
- Conditions
- Non-Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Peripheral T-cell Lymphoma
- Keywords
- NHL, DLBCL, PTCL, Marginal zone lymphoma, lymphoplasmacytic lymphoma, Waldenstrom's macroglobulinemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Study start
- Oct 2014
- Primary completion
- Mar 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 20 May 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 research study is evaluating a drug called carfilzomib used in combination with another drug called belinostat with participants who have relapsed or refractory non-Hodgkin lymphoma (NHL).
Detailed description
The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have NHL, not everyone who participates in this research study will receive the same dose of the study drug. The dose the each participant gets will depend on the number of participants who have been enrolled in the study prior and how the dose was tolerated.
- Study Drug(s): Both carfilzomib and belinostat will be given through a vein in the participant's arm (IV infusion). Each treatment cycle lasts 28 days (4 weeks).
- Carfilzomib will be given on Days 1-2, 8-9, and 15-16 of each cycle. The carfilzomib infusion will be given over about 10 minutes during the first cycle. However if the dose is increased over the course of the trial, or if in one of the groups that joins the study at a higher dose level, the infusion will last about 30 minutes. All participants will remain at the clinic under observation for at least 1 hour following each dose of carfilzomib during Cycle 1 and after the Cycle 2 Day 1 dose.
- Belinostat will be given on Days 1-5 of each cycle. The belinostat infusion will be given over about 30 minutes.
- Clinical Exams: During all cycles the participant will have a physical exam and will be asked questions about their general health and specific questions about any problems any medications you may be taking.
- Pharmacokinetic (PK) blood tests: One of the main reasons for this study is to find the highest dose of the study drug combination that can be used safely without experiencing severe side effects to use for future studies. Once this dose is found (the maximum tolerated dose, or MTD), additional blood samples will be drawn from a small set of participants (about 5 participants total) to learn more about the activity of the study drugs in the body over a period of time, including the ways the study drugs are absorbed, distributed, and then released from the body. If participating in this group (the participant will be informed from the Investigator) these pharmacokinetic (PK) samples will be drawn repeatedly over a period of 24 hours on certain days: Blood samples will be drawn at 0, 15, 30, 60, 90 minutes, and 2, 4, 6, 8 and 24 hours after the study drug dosing on Days 1-2, 4-5, and 9 of Cycle 1.
- Scans (or Imaging tests): Tumor assessment by CT or PET CT scans once every 8 weeks (every other cycle).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib/ Belinostat | Experimental | Drug: Carfilzomib, Drug: BelinostatCarfilzomib and Belinostat will be administered on a 28-day schedule. * Carfilzomib will be given on days 1-2, 8-9, and 15-16 of each cycle, beginning at a dose of 20 mg/m2 (dose level 0). * Belinostat will be given on days 1-5 beginning at a dose of 600 mg/m2. * Belinostat dosing will precede carfilzomib dosing on days when both drugs are administered. In dose level 1 and beyond, carfilzomib will be given at a dose of 20mg/m2 with cycle 1, and then escalated with cycle 2 * A maximum of four dose levels are planned with carfilzomib escalated no higher than 20/36 mg/m2 and belinostat escalated no higher than 900 mg/m2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Subjects must have histologically confirmed relapsed or refractory non-Hodgkin lymphoma that is not a candidate for standard curative therapy. NHL subtypes include: Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma, Marginal zone lymphoma, Lymphoplasmacytic lymphoma, Peripheral T-cell lymphomas, and Follicular lymphoma of any grade.
- Patients must have received at least one prior systemic therapy for lymphoma. A washout period of at least 3 weeks is required from the most recent prior therapy.
- Age ≥18 years
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A)
- Participants must have organ and marrow function as defined below:
Key exclusion criteria (19 listed)
- Participants who have had chemotherapy or radiotherapy within 3 weeks (8 weeks for radioimmunotherapy) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
- Participants who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib or belinostat
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
- Pregnant or lactating patients.
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® | Drug | Carfilzomib/ Belinostat |
| BelinostatAlso: Beleodaq | Drug | Carfilzomib/ Belinostat |
Primary outcome
Maximum tolerated doses of carfilzomib and belinostat in combination
Time frame: Baseline, 28 days
3 secondary outcomes
Number of Participants with Serious Adverse Events
Time frame: 28 days
Plasma Concentration Time Profiles
Time frame: 0, 5, 15, 30, 60, 90 min and 2, 4, 6, 8, and 24 hours
Objective response rate
Time frame: 8 Weeks
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 25 Jan 2018.
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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.
Jeremy Abramson, MD principal investigator
Massachusetts General Hospital
3 sites 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 Belinostat in people with Non-Hodgkin Lymphoma and Diffuse Large B-cell Lymphoma, run by Massachusetts General Hospital at 3 sites 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 16 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 25 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 doses of carfilzomib and belinostat in combination (time frame: Baseline, 28 days). 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 25 Jan 2018.