LymphomaPhase 1NCT01276717
Study of Carfilzomib and Vorinostat for Relapsed or Refractory Lymphoma
A Phase 1 study testing Drug: Carfilzomib and Vorinostat in people with Lymphoma, run by University of Rochester at 2 sites in United States.
Trial summary
This will be a phase I study of carfilzomib in combination with vorinostat in patients with relapsed/refractory B-cell lymphomas. Combination therapy with proteosome inhibitor PR-171 and HDAC inhibitors is highly synergistic in primary DLBCL cells, and both classes of drugs can also synergize powerfully to induce cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Drug: Carfilzomib and Vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2011to Jan 2015
- 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
- Histologically confirmed B-cell lymphomas, excluding CLL (Chronic Lymphocytic Leukemia), that is recurrent or refractory after at least one prior therapy and for which no other potentially curative therapy is available.
- Age ≥ 18 years
- ECOG Performance Status (PS) ≤ 2
- Laboratory parameters
- if SLL, lymphocyte count < 5,000/µL
- Absolute neutrophil count ≥ 1000/µL
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- Platelets ≥ 75,000/µL
- Creatinine ≤ 1.5x upper limit of normal or calculated creatinine clearance > 40mL/min
- AST, ALT ≤ 2.5 x upper limit of normal (ULN)
- Bilirubin ≤ 2.0 mg/mL
- Serum potassium ≥ 3.5 mEq/L and serum magnesium ≥ 1.7 mEq/dL (electrolytes may be corrected with supplementation).
- PT < 1.5 x ULN and PTT < 1.2 x ULN (unless receiving therapeutic anticoagulation).
- Patient is, in investigator's opinion, willing and able to comply with the protocol requirements and offers written informed consent.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control ( i.e., oral injectable hormonal methods; barrier methods such as intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence)for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of study.
Who cannot join
- History of brain metastasis including leptomeningeal metastasis.
- Chemotherapy of radiotherapy within 3 weeks prior to entering the study.
- Prior histone deacetylase inhibitor as cancer treatment.
- Concurrent treatment with other investigational agents or cancer treatment.
- Unable to take oral medications.
- Active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, left ventricular ejection fraction (LVEF) must be ≥ 45%, otherwise study to evaluate EF is not required.
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- Persistent blood pressure (BP) of ≥ 160/95 (three separate readings on different days).
- History of allergic reactions attributed to compounds of similar chemical or biological composition to carfilzomib and vorinostat.
- Known clinical significant infection including infection with human immunodeficiency virus (HIV), or active hepatitis B or C, requiring treatment.
- Serious medical or psychiatric illness likely to interfere with patient participation.
- Pregnant or nursing. Confirmation that a woman is not pregnant must be established by a negative serum pregnancy test result obtained at screening.
- Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- No prior allogeneic stem cell transplant.
- Patients scheduled for any type of stem cell transplant within 4 weeks of treatment.
- Patients who have valproic acid for epilepsy can enroll, provided that they stopped drug at least 30 days prior to enrollment and they will be on a stable, effective dose of an alternative anti-seizure medication.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298
University of Rochester
Rochester, New York, 14642
About this study
Official title: Phase I Trial of Carfilzomib (PR-171) in Combination With Vorinostat (SAHA) in Patients With Relapsed/Refractory B-Cell Lymphomas
This will be a phase I study of carfilzomib in combination with vorinostat in patients with relapsed/refractory B-cell lymphomas. Combination therapy with proteosome inhibitor PR-171 and HDAC inhibitors is highly synergistic in primary DLBCL cells, and both classes of drugs can also synergize powerfully to induce cell death in bortezomib-resistant cells. The purpose of this study is to see if vorinostat can combine with carfilzomib and to safely find the recommended phase II dose.
Read the detailed description
Study Drugs:
Vorinostat, a class I/II pan-histone deacetylase inhibitor (HDACI), was the first approved agent og this class on the basis of activity in refractory cutaneous T-cell Lymphoma. Lethal mechanisms include anti-apoptotic protein down-regulation, up-regulation of proapoptotic proteins, induction of ROS, death receptor up-regulation, and disruption of chaperone function and DNA-repair proteins.
Carfilzomib, is a irreversible proteasome inhibitor of the epoxyketone class that exhibits a high level of selectivity for the proteosome. This agent induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis.
Study Drug Administration:
If you are found to be eligible to take part in this study:
- Vorinostat PO twice daily on Days 1, 2, 3, 8, 9, 10, 15, 16 and 17.
- Daily Carfilzomib 30 minutes infusion on Days 1, 2, 8, 9, 15, 16.
- Administer first daily dose of vorinostat prior to carfilzomib on Days 1, 2, 8, 9, 15, 16
- Cycle repeated every 28 days, up to 13 cycles.
Carfilzomib will be given at 20mg/m2 for days 1 and 2 of cycle 1 only, then escalated to the higher dose indicated in the schema on day 8 of cycle 1 and thereafter. Carfilzomib treatment is to be done early in the morning and have a minimum of a 6 hour observation period after the infusion. For patients with good tolerability to carfilzomib during the first cycle, an observation period of 2 hours is recommended. A minimum of 16 hours should separate doses of carfilzomib, so that the day 1 dose may be given in the afternoon and the day 2 dose in morning during cycle 2 and subsequent cycles for patients who tolerate the drug well.
If two out of 6 patients do not tolerate the initial dose of 20 mg/m2 carfilzomib on days 1 \& 2 followed by 27 mg/m2 carfilzomib for subsequent doses and 200 mg/day bid vorinostat, the next patient should be dose reduced to 20 mg/m2 carfilzomib and 100 mg/day bid vorinostat.
Study Visits:
- Baseline within 4 weeks of Cycle 1 Day 1.
- CT or physical exam.
- Bone marrow if needed to follow disease status.
- PET recommended but not required. To document complete response (CR), a PET is REQUIRED.
- Optional research tumor biopsy.
- Peripheral blood obtained for PD prior to initiation of treatment and at 48 hours +/- 6 hours after receiving first dose of Carfilzomib , and at Off Study.
- End of Treatment Restaging will take place 6-8 weeks after completion of treatment and will include an assessment by the physician, labs, and a tumor response evaluation.
- After completion of Restaging exams, Follow up exams will take place every 6 months for 2 years and then annually until disease progression or initiation of another treatment.
- An Off Study visit will take place at the time of disease progression or initiation of another treatment, which will include assessment by the physician,a tumor response evaluation, labs, and a final PD sample, by the patient's consent.
- Conditions
- Lymphoma
- Being tested
- Drug: Carfilzomib, Vorinostat
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: CarfilzomibDrug
Also called PR-171
Carfilzomib 30 minutes infusion daily for days 1, 2, 8, 9, 15, 16, Every 28 days. A maximum of 13 cycles will be administered.
VorinostatDrug
Also called Zolinza®
Vorinostat by mouth twice daily on days 1, 2, 3, 8, 9, 10, 15, 16 and 17. Maximum 13 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat + Carfilzomib | Experimental | Not described Receives: Drug: Drug: Carfilzomib; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants who experience Adverse Events as a Measure of Safety and Tolerability
Determine the recommended phase II doses for the combination of carfilzomib and vorinostat in patients with relapsed or refractory B cell lymphoma.
Measured: From date of study entry until the 30 days after the last dose of study treatment.
Secondary outcomes (1)
Number of Participants who Respond to Treatment
Determine response rate to combination of carfilzomib and vorinostat.
Measured: From the date of completion of first cycle of treatment until the date of best response to treatment, as determined by restaging scans
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionJul 2013
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- Massey Cancer Center
- Responsible party
- Principal investigator, Jonathan Friedberg, University of Rochester
- Investigators
- Jonathan Friedberg, M.D., Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276717
- Sponsor's protocol ID
- 32833
- Status last verified
- Dec 2015
- First submitted
- 10 Nov 2010
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Carfilzomib (PR-171) in Combination With Vorinostat (SAHA) in Patients With Relapsed/Refractory B-Cell Lymphomas
- ClinicalTrials.gov ID
- NCT01276717
- Acronym / sponsor ID
- 32833
- Conditions
- Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- Massey Cancer Center
- Study start
- Jan 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 13 Jan 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 will be a phase I study of carfilzomib in combination with vorinostat in patients with relapsed/refractory B-cell lymphomas. Combination therapy with proteosome inhibitor PR-171 and HDAC inhibitors is highly synergistic in primary DLBCL cells, and both classes of drugs can also synergize powerfully to induce cell death in bortezomib-resistant cells. The purpose of this study is to see if vorinostat can combine with carfilzomib and to safely find the recommended phase II dose.
Detailed description
Study Drugs:
Vorinostat, a class I/II pan-histone deacetylase inhibitor (HDACI), was the first approved agent og this class on the basis of activity in refractory cutaneous T-cell Lymphoma. Lethal mechanisms include anti-apoptotic protein down-regulation, up-regulation of proapoptotic proteins, induction of ROS, death receptor up-regulation, and disruption of chaperone function and DNA-repair proteins.
Carfilzomib, is a irreversible proteasome inhibitor of the epoxyketone class that exhibits a high level of selectivity for the proteosome. This agent induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis.
Study Drug Administration:
If you are found to be eligible to take part in this study:
- Vorinostat PO twice daily on Days 1, 2, 3, 8, 9, 10, 15, 16 and 17.
- Daily Carfilzomib 30 minutes infusion on Days 1, 2, 8, 9, 15, 16.
- Administer first daily dose of vorinostat prior to carfilzomib on Days 1, 2, 8, 9, 15, 16
- Cycle repeated every 28 days, up to 13 cycles.
Carfilzomib will be given at 20mg/m2 for days 1 and 2 of cycle 1 only, then escalated to the higher dose indicated in the schema on day 8 of cycle 1 and thereafter. Carfilzomib treatment is to be done early in the morning and have a minimum of a 6 hour observation period after the infusion. For patients with good tolerability to carfilzomib during the first cycle, an observation period of 2 hours is recommended. A minimum of 16 hours should separate doses of carfilzomib, so that the day 1 dose may be given in the afternoon and the day 2 dose in morning during cycle 2 and subsequent cycles for patients who tolerate the drug well.
If two out of 6 patients do not tolerate the initial dose of 20 mg/m2 carfilzomib on days 1 \& 2 followed by 27 mg/m2 carfilzomib for subsequent doses and 200 mg/day bid vorinostat, the next patient should be dose reduced to 20 mg/m2 carfilzomib and 100 mg/day bid vorinostat.
Study Visits:
- Baseline within 4 weeks of Cycle 1 Day 1.
- CT or physical exam.
- Bone marrow if needed to follow disease status.
- PET recommended but not required. To document complete response (CR), a PET is REQUIRED.
- Optional research tumor biopsy.
- Peripheral blood obtained for PD prior to initiation of treatment and at 48 hours +/- 6 hours after receiving first dose of Carfilzomib , and at Off Study.
- End of Treatment Restaging will take place 6-8 weeks after completion of treatment and will include an assessment by the physician, labs, and a tumor response evaluation.
- After completion of Restaging exams, Follow up exams will take place every 6 months for 2 years and then annually until disease progression or initiation of another treatment.
- An Off Study visit will take place at the time of disease progression or initiation of another treatment, which will include assessment by the physician,a tumor response evaluation, labs, and a final PD sample, by the patient's consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat + Carfilzomib | Experimental | Drug: Drug: Carfilzomib, Drug: Vorinostat |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed B-cell lymphomas, excluding CLL (Chronic Lymphocytic Leukemia), that is recurrent or refractory after at least one prior therapy and for which no other potentially curative therapy is available.
- Age ≥ 18 years
- ECOG Performance Status (PS) ≤ 2
- Laboratory parameters
- Patient is, in investigator's opinion, willing and able to comply with the protocol requirements and offers written informed consent.
Key exclusion criteria (15 listed)
- History of brain metastasis including leptomeningeal metastasis.
- Chemotherapy of radiotherapy within 3 weeks prior to entering the study.
- Prior histone deacetylase inhibitor as cancer treatment.
- Concurrent treatment with other investigational agents or cancer treatment.
- Unable to take oral medications.
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 |
|---|---|---|
| Drug: CarfilzomibAlso: PR-171Carfilzomib 30 minutes infusion daily for days 1, 2, 8, 9, 15, 16, Every 28 days. A maximum of 13 cycles will be administered. | Drug | Vorinostat + Carfilzomib |
| VorinostatAlso: Zolinza®Vorinostat by mouth twice daily on days 1, 2, 3, 8, 9, 10, 15, 16 and 17. Maximum 13 cycles. | Drug | Vorinostat + Carfilzomib |
Primary outcome
Number of Participants who experience Adverse Events as a Measure of Safety and Tolerability
Time frame: From date of study entry until the 30 days after the last dose of study treatment.
Determine the recommended phase II doses for the combination of carfilzomib and vorinostat in patients with relapsed or refractory B cell lymphoma.
1 secondary outcome
Number of Participants who Respond to Treatment
Time frame: From the date of completion of first cycle of treatment until the date of best response to treatment, as determined by restaging scans
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 3 Dec 2015.
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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.
Jonathan Friedberg, M.D. principal investigator
University of Rochester
2 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 Drug: Carfilzomib and Vorinostat in people with Lymphoma, run by University of Rochester at 2 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 15 inclusion and 15 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 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Number of Participants who experience Adverse Events as a Measure of Safety and Tolerability (time frame: From date of study entry until the 30 days after the last dose of study treatment.). 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 3 Dec 2015.