LymphomaPhase 1NCT01926665
Carfilzomib Consolidation Therapy After Autologous Stem Cell Transplantation (ASCT) for Mantle Cell Lymphoma (MCL), T-cell Lymphoma (TCL), and Diffuse Large B-Cell Lymphoma (DLBCL)
A Phase 1 study testing Carfilzomib and Dexamethasone in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of carfilzomib that can be given to patients with lymphoma after a stem cell transplant. The safety of this drug will also be studied. Carfilzomib is designed to block cancer cells from repairing themselves. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- Carfilzomib and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jun 2014to 17 Sep 2017
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with mantle cell lymphoma, T-cell lymphoma, and diffuse large b-cell lymphoma within 6 months post autologous transplantation and without relapse.
- Age >/= 18 years to </= 70 years.
- Absolute neutrophil count (ANC) >/= to 1.5 x 10^9/L; Platelets > 75 x 10^9/L.
- No active infection.
- Performance status: Eastern Cooperative Oncology Group (ECOG) 2 or less or Karnofsky of at least 60.
- Cardiac EF >/= 45% by 2D-Echo.
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- Serum creatinine less than 1.6 mg/dl and Creatinine Clearance >/= to 30 mL/min.
- Liver function tests less than 2x upper limit of normal range (unless related to medications or Gilbert's disease).
- Females of childbearing potential who are not pregnant or breastfeeding.
- Patient or legally authorized representative able to sign informed consent.
Who cannot join
- Glucocorticoid therapy (prednisone >30 mg/day or equivalent within 14 days of first dose.
- POEMS syndrome.
- Plasma cell leukemia or circulating plasma cells >/= 2 X 10^9/L.
- Waldenstrom's Macroglobulinemia.
- Patients with known amyloidosis.
- Immunotherapy or chemotherapy with approved or investigational anticancer therapeutics within 21 days of first dose.
Show all 18Show fewer
- Patients previously randomized in any other Onyx-sponsored Phase 3 trial.
- Active congestive heart failure (NYHA Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months.
- Acute active infection requiring systemic antibiotics, antiviral (except antiviral directed at Hepatitis B) or antifungal agents within 14 days of first dose.
- Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B SAg or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
- Patients with known cirrhosis.
- Second malignancy within past three years except: a. adequately treated basal or squamous cell skin cancer. b. carcinoma in situ of the cervix. c. prostate cancer < Gleason Score 6 with stable prostatic specific antigen (PSA) over the past three months. d. breast cancer in situ with full surgical resection. e. treated medullary or papillary thyroid cancer.
- Patients with myelodysplastic syndrome.
- Significant neuropathy (Grades 3 to 4, or Grade 2 pain).
- Known hypersensitivity to carfilzomib.
- Known contraindication to dexamethasone.
- Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days of first dose.
- Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol compliance.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Carfilzomib Consolidation Therapy After Autologous Stem Cell Transplantation (ASCT) for Patients With Mantle Cell (MCL), T-cell (TCL), and Diffuse B-Cell Lymphoma (DLBCL)
The goal of this clinical research study is to find the highest tolerable dose of carfilzomib that can be given to patients with lymphoma after a stem cell transplant. The safety of this drug will also be studied.
Carfilzomib is designed to block cancer cells from repairing themselves. If the cancer cells cannot repair themselves, this may cause them to die.
Read the detailed description
Study Groups:
If you agree to take part in this study, you will be assigned to a dose level of carfilzomib based on when you joined this study. Up to 4 dose levels of carfilzomib will be tested. Three (3) participants will be enrolled at each dose level until the highest tolerable dose level is found. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. When the highest tolerable dose is found, more participants may be enrolled at that dose level.
Study Treatment:
Each study cycle is 28 days.
On Days 1, 2, 15, and 16 of each cycle, you will receive carfilzomib by vein over 30 minutes. You will receive hydration by vein before and after each infusion of carfilzomib in Cycle 1. This may be repeated in Cycle 2, if your doctor thinks it is needed. On these days during Cycles 1 and 2, before you receive carfilzomib you will receive dexamethasone by vein or as a tablet by mouth. Dexamethasone may help prevent possible infusion reactions. You may continue to receive dexamethasone before each dose of each cycle depending how well you tolerate the infusion.
You will be monitored closely for at least 1 hour for possible infusion reactions after each dose during Cycle 1 and on Day 1 of Cycle 2. If you have an infusion reaction, your doctor may delay or stop the infusion, and you may receive drugs to help relieve the symptoms.
You will have about 12 days of "rest" between each cycle of treatment (during this time you will not receive carfilzomib).
Study Visits:
On Day 1 (+ or - 3 days) of Cycle 1 and on Day 1 of all other cycles, women who are able to become pregnant will have blood (about 1 teaspoon) drawn for a pregnancy test. To take part in this study, you must not be pregnant.
About 1 day before you receive carfilzomib in each cycle:
- You will have a physical exam including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
- You will be asked about how you are feeling and about any side effects you may be having.
About 1 day and about 15 days before you receive carfilzomib in each cycle, blood (about 2 tablespoons) will be drawn for routine tests and to check your kidney and liver function.
At any point that your doctor thinks they are needed, you will have a bone marrow aspiration and computed tomography (CT) and/or positron emission tomography (PET) scans to check the status of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
End-of-Treatment Visit:
Within 30 days of your last dose of study drug, you will return to the clinic. The following tests and procedures will be performed:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about how you are feeling and about any side effects you may be having.
- Blood (about 4 tablespoons) will be drawn for routine tests and to check the status of the disease.
During follow-up, the study staff may also contact you and your local doctor by telephone to ask about your health.
Length of Study:
You may remain in this study for about 2 years from the time of first dose. You may receive up to 6 cycles of treatment during this time, which will take about 7 months to complete. You will be taken off study early if the disease gets worse, you cannot keep appointments, you miss more than 2 doses of carfilzomib in a row, if intolerable side effects occur, or if you decide that you want to leave the study early.
This is an investigational study. Carfilzomib is FDA approved and commercially available for the treatment of multiple myeloma. The use of carfilzomib to treat lymphoma after a stem cell transplant is investigational.
Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.
- Conditions
- Lymphoma
- Being tested
- Carfilzomib, Dexamethasone
- Keywords
- Blood And Marrow Transplantation, Mantle cell lymphoma, MCL, T-cell lymphoma, TCL, Diffuse large b-cell lymphoma, DLBCL, Autologous stem cell transplantation, ASCT, Carfilzomib, CFZ, Dexamethasone, Decadron
- Medical subject headings
- Lymphoma, Lymphoma, Mantle-Cell, Lymphoma, T-Cell, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Starting dose: 20/20 mg/m2 by vein on Days 1, 2, 15, and 16 of each 28 day cycle.
DexamethasoneDrug
Also called Decadron
4 mg by vein or mouth prior to each Carfilzomib dose in Cycle 1 and 2 to prevent infusion reactions. After dexamethasone is stopped, it should be restarted and administered prior to subsequent doses for reactions.
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib | Experimental | Carfilzomib given in four doses, days 1, 2, 15 and 16, every 28 days for 6 months starting within 6 months post ASCT. Doses given in an escalated phase 1 design, starting at 20/20 mg/m2, later increased to 20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2. CFZ dose based on actual body surface area at baseline (cycle 1). Patients with a body surface area (BSA) greater than 2.2 m2 receive dose based upon a 2.2 m2 BSA. Adjustments are not made if weight gains or losses are less than or equal to 20% from baseline. Dexamethasone 4 mg by vein or mouth prior to each CFZ dose in cycle 1 and 2 to prevent infusion reactions. After dexamethasone is stopped, then it should be restarted and administered prior to subsequent doses for reactions. Receives: 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 (CFZ) After Autologous Stem Cell Transplantation (ASCT)
Maximum tolerated dose (MTD) defined as dose with a posterior probability of treatment-related dose-limiting toxicity (DLT) during the first 56 days closest to the target of 30%. DLT defined as: equal or greater than Grade (G) 2 neuropathy with pain, equal or greater than G3 non-hematologic toxicity, G4 neutropenia greater than 7 days, febrile neutropenia, G4 thrombocytopenia lasting for more than 7 days despite withholding CFZ, G3/4 thrombocytopenia with bleeding, or equal or greater than Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal by day 56.
Measured: 56 days
Secondary outcomes (1)
Efficacy of Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT)
Efficacy assessed by progression free survival (PFS) and overall survival (OS) at 2 years. Assess progression rate and correlations with Ki67, and gene profiling. Distributions of PFS and OS estimated by Kaplan-Meier method, and distributions compared between groups by using the log-rank test. Cox proportional hazards regression models will be fit to assess the relationship between baseline covariates of interest and these survival parameters.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2013 (estimated)
- Study start17 Jun 2014
- Primary completion17 Sep 2017
- Study completion17 Sep 2017
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 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Issa F. Khouri, MD,BS, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01926665
- Sponsor's protocol ID
- 2012-1070
- Other IDs
- NCI-2014-00994
- Status last verified
- Sep 2017
- First submitted
- 19 Aug 2013
- Last updated
- 19 Sep 2017
- 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 19 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carfilzomib Consolidation Therapy After Autologous Stem Cell Transplantation (ASCT) for Patients With Mantle Cell (MCL), T-cell (TCL), and Diffuse B-Cell Lymphoma (DLBCL)
- ClinicalTrials.gov ID
- NCT01926665
- Acronym / sponsor ID
- 2012-1070
- Conditions
- Lymphoma
- Keywords
- Blood And Marrow Transplantation, Mantle cell lymphoma, MCL, T-cell lymphoma, TCL, Diffuse large b-cell lymphoma, DLBCL, Autologous stem cell transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 17 Jun 2014 (actual)
- Primary completion
- 17 Sep 2017 (actual)
- Study completion
- 17 Sep 2017 (actual)
- First posted
- 21 Aug 2013 (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.
The goal of this clinical research study is to find the highest tolerable dose of carfilzomib that can be given to patients with lymphoma after a stem cell transplant. The safety of this drug will also be studied.
Carfilzomib is designed to block cancer cells from repairing themselves. If the cancer cells cannot repair themselves, this may cause them to die.
Detailed description
Study Groups:
If you agree to take part in this study, you will be assigned to a dose level of carfilzomib based on when you joined this study. Up to 4 dose levels of carfilzomib will be tested. Three (3) participants will be enrolled at each dose level until the highest tolerable dose level is found. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. When the highest tolerable dose is found, more participants may be enrolled at that dose level.
Study Treatment:
Each study cycle is 28 days.
On Days 1, 2, 15, and 16 of each cycle, you will receive carfilzomib by vein over 30 minutes. You will receive hydration by vein before and after each infusion of carfilzomib in Cycle 1. This may be repeated in Cycle 2, if your doctor thinks it is needed. On these days during Cycles 1 and 2, before you receive carfilzomib you will receive dexamethasone by vein or as a tablet by mouth. Dexamethasone may help prevent possible infusion reactions. You may continue to receive dexamethasone before each dose of each cycle depending how well you tolerate the infusion.
You will be monitored closely for at least 1 hour for possible infusion reactions after each dose during Cycle 1 and on Day 1 of Cycle 2. If you have an infusion reaction, your doctor may delay or stop the infusion, and you may receive drugs to help relieve the symptoms.
You will have about 12 days of "rest" between each cycle of treatment (during this time you will not receive carfilzomib).
Study Visits:
On Day 1 (+ or - 3 days) of Cycle 1 and on Day 1 of all other cycles, women who are able to become pregnant will have blood (about 1 teaspoon) drawn for a pregnancy test. To take part in this study, you must not be pregnant.
About 1 day before you receive carfilzomib in each cycle:
- You will have a physical exam including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
- You will be asked about how you are feeling and about any side effects you may be having.
About 1 day and about 15 days before you receive carfilzomib in each cycle, blood (about 2 tablespoons) will be drawn for routine tests and to check your kidney and liver function.
At any point that your doctor thinks they are needed, you will have a bone marrow aspiration and computed tomography (CT) and/or positron emission tomography (PET) scans to check the status of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
End-of-Treatment Visit:
Within 30 days of your last dose of study drug, you will return to the clinic. The following tests and procedures will be performed:
- You will have a physical exam, including measurement of your vital signs.
- You will be asked about how you are feeling and about any side effects you may be having.
- Blood (about 4 tablespoons) will be drawn for routine tests and to check the status of the disease.
During follow-up, the study staff may also contact you and your local doctor by telephone to ask about your health.
Length of Study:
You may remain in this study for about 2 years from the time of first dose. You may receive up to 6 cycles of treatment during this time, which will take about 7 months to complete. You will be taken off study early if the disease gets worse, you cannot keep appointments, you miss more than 2 doses of carfilzomib in a row, if intolerable side effects occur, or if you decide that you want to leave the study early.
This is an investigational study. Carfilzomib is FDA approved and commercially available for the treatment of multiple myeloma. The use of carfilzomib to treat lymphoma after a stem cell transplant is investigational.
Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib | Experimental | Drug: Carfilzomib, Drug: DexamethasoneCarfilzomib given in four doses, days 1, 2, 15 and 16, every 28 days for 6 months starting within 6 months post ASCT. Doses given in an escalated phase 1 design, starting at 20/20 mg/m2, later increased to 20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2. CFZ dose based on actual body surface area at baseline (cycle 1). Patients with a body surface area (BSA) greater than 2.2 m2 receive dose based upon a 2.2 m2 BSA. Adjustments are not made if weight gains or losses are less than or equal to 20% from baseline. Dexamethasone 4 mg by vein or mouth prior to each CFZ dose in cycle 1 and 2 to prevent infusion reactions. After dexamethasone is stopped, then it should be restarted and administered prior to subsequent doses for reactions. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with mantle cell lymphoma, T-cell lymphoma, and diffuse large b-cell lymphoma within 6 months post autologous transplantation and without relapse.
- Age >/= 18 years to </= 70 years.
- Absolute neutrophil count (ANC) >/= to 1.5 x 10^9/L; Platelets > 75 x 10^9/L.
- No active infection.
- Performance status: Eastern Cooperative Oncology Group (ECOG) 2 or less or Karnofsky of at least 60.
Key exclusion criteria (18 listed)
- Glucocorticoid therapy (prednisone >30 mg/day or equivalent within 14 days of first dose.
- POEMS syndrome.
- Plasma cell leukemia or circulating plasma cells >/= 2 X 10^9/L.
- Waldenstrom's Macroglobulinemia.
- Patients with known amyloidosis.
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 |
|---|---|---|
| CarfilzomibStarting dose: 20/20 mg/m2 by vein on Days 1, 2, 15, and 16 of each 28 day cycle. | Drug | Carfilzomib |
| DexamethasoneAlso: Decadron4 mg by vein or mouth prior to each Carfilzomib dose in Cycle 1 and 2 to prevent infusion reactions. After dexamethasone is stopped, it should be restarted and administered prior to subsequent doses for reactions. | Drug | Carfilzomib |
Primary outcome
Maximum Tolerated Dose (MTD) of Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT)
Time frame: 56 days
Maximum tolerated dose (MTD) defined as dose with a posterior probability of treatment-related dose-limiting toxicity (DLT) during the first 56 days closest to the target of 30%. DLT defined as: equal or greater than Grade (G) 2 neuropathy with pain, equal or greater than G3 non-hematologic toxicity, G4 neutropenia greater than 7 days, febrile neutropenia, G4 thrombocytopenia lasting for more than 7 days despite withholding CFZ, G3/4 thrombocytopenia with bleeding, or equal or greater than Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal by day 56.
1 secondary outcome
Efficacy of Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT)
Time frame: 2 years
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 19 Sep 2017.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Issa F. Khouri, MD,BS 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 Dexamethasone in people with Lymphoma, 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 10 inclusion and 18 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 19 Sep 2017. 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 Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT) (time frame: 56 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 19 Sep 2017.