Lymphoma, Mantle CellPhase 2NCT00114738
EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma
A Phase 2 study testing Rituximab (R), EPOCH and Bortezomib (B) in people with Lymphoma, Mantle Cell and Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will evaluate the effectiveness of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) chemotherapy plus bortezomib for treating mantle cell lymphoma, a cancer of white blood cells called lymphocytes. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Lymphoma, Mantle Cell, Mantle Cell Lymphoma
- What is being tested?
- Rituximab (R), EPOCH and Bortezomib (B)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2005to 11 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
- ELIGIBILITY CRITERIA:
Diagnosis of mantle cell lymphoma (confirmed at National Cancer Institute (NCI)). All variants are eligible.
Age greater than or equal to 18 years.
No prior treatment except for local radiation or a short course of steroids for control of symptoms.
All stages of disease.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3.
Adequate major organ function (serum creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 50 ml/min; bilirubin less than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated; Absolute neutrophil count (ANC) greater than 1000 and platelets greater than 75,000) unless impairment due to organ involvement by lymphoma.
No myocardial infarction within 6 months prior to enrollment or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.
No grade 2 greater than or equal to peripheral neuropathy within 14 days before enrollment.
Ability to give informed consent.
Human immunodeficiency virus (HIV) antibody negative.
Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Female subject is not pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-human chorionic gonadotropin (hCG)) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
Male subject agrees to use an acceptable method for contraception for the duration of the study.
No history of a prior invasive malignancy in past 5 years
No known involvement of central nervous system by lymphoma
No history of hypersensitivity to boron or mannitol.
Patient has not received other investigational drugs with 14 days before enrollment.
No serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Exclusion for fludeoxyglucose (FDG) scan is anyone exceeding the weight limit of the scanner (350 lb).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib (EPOCH-R-B) Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics
This study will evaluate the effectiveness of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) chemotherapy plus bortezomib for treating mantle cell lymphoma, a cancer of white blood cells called lymphocytes. EPOCH-R consists of the drugs prednisone, etoposide, doxorubicin and vincristine, with the addition of a new drug called rituximab. In a recent study of patients with newly diagnosed mantle cell lymphoma, 92 percent had a complete remission of their disease after treatment with EPOCH-R. This study will test whether adding bortezomib as "maintenance therapy" once chemotherapy is finished will lengthen the time before the disease relapses and improve the overall cure rate.
Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, multi-gated acquisition scan (MUGA) or echocardiogram, imaging studies and biopsy to determine the extent of disease, and possible colonoscopy.
Read more
Participants undergo treatment in three parts, as follows:
- Part 1: Bortezomib alone: Patients receive 4 doses of bortezomib over 3 weeks. The drug is injected into a vein over about 30 seconds.
- Part 2: EPOCH-R chemotherapy plus bortezomib: This phase of treatment begins 3 to 4 weeks after completing Part 1. Treatment is given on an outpatient basis in six 3-week cycles, with all drugs administered over the first 5 days of each cycle. Patients take prednisone by mouth on days 1 to 5 and etoposide, doxorubicin, and vincristine as a 96-hour infusion through a vein over days 1 to 5. The infused drugs are delivered through a lightweight, portable infusion pump. Rituximab is given by vein over several hours on day 1 immediately before the chemotherapy infusion begins. Bortezomib is given by vein over 30 seconds on day 1 before the rituximab and again on day 4. Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the chemotherapy infusion is completed. Patients are taught how to self inject granulocyte colony stimulating factor (G-CSF), a drug that helps boost white cell counts after chemotherapy. They inject the drug under the skin (like an insulin shot) for 10 days of each cycle beginning day 6. Patients also take an antibiotic to help prevent infection during chemotherapy.
- Part 3: Bortezomib alone: After completing EPOCH-R-B therapy, patients are randomly assigned to receive or not to receive bortezomib alone. The drug is given in 2 doses over 5 days, with a break of 16 days before the next dose. These 3-week cycles continue for up to 18 months or until the disease comes back or worsens. Patients who are assigned to the group that does not receive bortezomib will be offered the drug if their disease relapses.
During therapy, patients have tests performed on their bone marrow, tumor tissue, blood or other fluids to look at different genes and proteins that may be involved in the development of their lymphoma or the reaction of the immune system. A tissue biopsy is done before treatment begins and a day after treatment starts. Disease progress is followed with computed tomography (CT) scans and blood tests. When treatment is completed, patients whose cancer has disappeared are scheduled for periodic follow-up examinations and tests. Those whose disease remains or recurs may be offered participation in another protocol if an appropriate one is available or are returned to the care of their local physician.
...
Read the detailed description
Background:
Mantle cell lymphoma (MCL) presents a clinical challenge because it is aggressive and incurable with chemotherapy. Therefore novel treatment approaches are needed.
MCL has overexpression of NF-kappa B (NF-kappa B), a transcription factor that affects cell growth and survival, and cyclin D1 that affects cell cycle and growth. These proteins appear to be involved in the pathogenesis of MCL.
Bortezomib, a proteasome inhibitor that inhibits NF-kappa B and cyclin D1, has demonstrated activity in patients with relapsed or refractory MCL.
Dose-adjusted-etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) has excellent activity in MCL, with a complete response (CR) rate of 92%, but patients eventually relapse.
Objective:
Determine the progression free survival (PFS) and overall survival (OS) of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab,bortezomib (DA-EPOCH-RB) followed by bortezomib maintenance versus observation.
Eligibility:
Diagnosis of mantle cell lymphoma.
No prior treatment except for local radiation or a short course of steroids for control of symptoms,
Age greater than or equal to 18 years old.
Adequate major organ function unless impairment is due to lymphoma.
Study Design:
To assess the clinical activity and biological effects of bortezomib, patients will initially receive one cycle of bortezomib alone with sequential tumor biopsies for microarray analysis.
All patients will then receive Dose-adjusted (DA)-EPOCH-RB for 6 cycles, and if they have at least a PR, this will be followed by randomization to either immediate bortezomib maintenance x 18 months, or to observation, followed by bortezomib if progression occurs. This study has as a primary goal, to describe progression free survival (PFS) and overall survival of early bortezomib maintenance versus observation following induction with bortezomib followed by DA-EPOCH-RB. Important secondary goals are to assess response and toxicity to bortezomib alone or DA-EPOCH-RB, to evaluate time to progression after receiving bortezomib following progression on an observation arm, and to assess the biological effects of bortezomib on untreated MCL.
- Conditions
- Lymphoma, Mantle Cell, Mantle Cell Lymphoma
- Being tested
- Rituximab (R), EPOCH, Bortezomib (B), Bortezomib, Bortezomib or observation
- Keywords
- Proteasome Inhibition, NF-Kappa-B, Gene Expression Signature, Cyclin D1, Translational Studies, Lymphoma, Mantle Cell Lymphoma, MCL
- Medical subject headings
- Lymphoma, Mantle-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab (R)Drug
Also called Rituxan
Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.
EPOCHBiological
EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.
Bortezomib (B)Drug
Also called Velcade
Bortezomib is given alone for one cycle.
BortezomibDrug
Also called Velcade
Bortezomib is given with EPOCH and rituximab every 6 weeks for 12 cycles.
Bortezomib or observationDrug
Also called Velcade
At the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib.
| Study group | Role | What they receive |
|---|---|---|
| EPOCH-R + Bortezomib | Experimental | Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B) Receives: Drug: Rituximab (R); Biological: EPOCH; Drug: Bortezomib |
| Bortezomib "window" | Experimental | Bortezomib alone Receives: Drug: Bortezomib (B) |
| Bortezomib maintenance | Active comparator | Bortezomib maintenance Receives: Drug: Bortezomib |
| Observation | Other | At the beginning of part C patients are randomized to receive bortezomib maintenance or observation without bortezomib. Receives: Drug: Bortezomib or observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Measured: up to 5 years
Median Overall Survival (OS)
Overall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Measured: up to 9.9 years
Overall Progression Free Survival
Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.
Measured: up to 9.9 years
Overall Survival
Overall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Measured: up to 9.9 years
Secondary outcomes (2)
Count of Participants With Serious and Non-Serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Measured: Date treatment consent signed to date off study, approximately 143 months and 7 days
Clinical Response
Clinical response is assessed by the response criteria for lymphomas and is defined as a fraction of patients who have a complete response (CR) or a complete response (CR) + partial response (PR). A complete response is disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g. lactate dehydrogenase) definitely assignable to the lymphoma. Partial response is ≥50% decreased in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Progressive disease is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen, ≥50% increase in the absolute number of circulating lymphocytes.
Measured: up to 22 weeks after initiation of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2005 (estimated)
- Study start15 Jun 2005
- Primary completion11 Aug 2016
- Study completion11 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Mantle CellStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Wyndham Wilson, M.D., National Cancer Institute (NCI)
- Investigators
- Wyndham H Wilson, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00114738
- Sponsor's protocol ID
- 050170
- Other IDs
- 05-C-0170
- Status last verified
- Sep 2022
- First submitted
- 17 Jun 2005
- Last updated
- 10 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Velders GA, Kluin-Nelemans JC, De Boer CJ, Hermans J, Noordijk EM, Schuuring E, Kramer MH, Van Deijk WA, Rahder JB, Kluin PM, Van Krieken JH. Mantle-cell lymphoma: a population-based clinical study. J Clin Oncol. 1996 Apr;14(4):1269-74. doi: 10.1200/JCO.1996.14.4.1269.
PubMed 8648383Campo E, Raffeld M, Jaffe ES. Mantle-cell lymphoma. Semin Hematol. 1999 Apr;36(2):115-27.
PubMed 10319380Hiddemann W, Unterhalt M, Herrmann R, Woltjen HH, Kreuser ED, Trumper L, Reuss-Borst M, Terhardt-Kasten E, Busch M, Neubauer A, Kaiser U, Hanrath RD, Middeke H, Helm G, Freund M, Stein H, Tiemann M, Parwaresch R. Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol. 1998 May;16(5):1922-30. doi: 10.1200/JCO.1998.16.5.1922.
PubMed 9586911Lakhotia R, Melani C, Dunleavy K, Pittaluga S, Saba N, Lindenberg L, Mena E, Bergvall E, Lucas AN, Jacob A, Yusko E, Steinberg SM, Jaffe ES, Wiestner A, Wilson WH, Roschewski M. Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma. Blood Adv. 2022 Apr 26;6(8):2667-2680. doi: 10.1182/bloodadvances.2021006397.
PubMed 35143622Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, Kuil A, Herman SE, Chang S, Pals ST, Wilson W, Wiestner A, Spaargaren M, Buggy JJ, Elias L. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013 Oct 3;122(14):2412-24. doi: 10.1182/blood-2013-02-482125. Epub 2013 Aug 12.
PubMed 23940282Perez-Galan P, Mora-Jensen H, Weniger MA, Shaffer AL 3rd, Rizzatti EG, Chapman CM, Mo CC, Stennett LS, Rader C, Liu P, Raghavachari N, Stetler-Stevenson M, Yuan C, Pittaluga S, Maric I, Dunleavy KM, Wilson WH, Staudt LM, Wiestner A. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation. Blood. 2011 Jan 13;117(2):542-52. doi: 10.1182/blood-2010-02-269514. Epub 2010 Oct 18.
PubMed 20956803
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib (EPOCH-R-B) Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics
- ClinicalTrials.gov ID
- NCT00114738
- Acronym / sponsor ID
- 050170
- Conditions
- Lymphoma, Mantle Cell, Mantle Cell Lymphoma
- Keywords
- Proteasome Inhibition, NF-Kappa-B, Gene Expression Signature, Cyclin D1, Translational Studies, Lymphoma, Mantle Cell Lymphoma, MCL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Jun 2005 (actual)
- Primary completion
- 11 Aug 2016 (actual)
- Study completion
- 11 Aug 2022 (actual)
- First posted
- 17 Jun 2005 (estimated)
- Results
- Posted 3 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effectiveness of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) chemotherapy plus bortezomib for treating mantle cell lymphoma, a cancer of white blood cells called lymphocytes. EPOCH-R consists of the drugs prednisone, etoposide, doxorubicin and vincristine, with the addition of a new drug called rituximab. In a recent study of patients with newly diagnosed mantle cell lymphoma, 92 percent had a complete remission of their disease after treatment with EPOCH-R. This study will test whether adding bortezomib as "maintenance therapy" once chemotherapy is finished will lengthen the time before the disease relapses and improve the overall cure rate.
Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, multi-gated acquisition scan (MUGA) or echocardiogram, imaging studies and biopsy to determine the extent of disease, and possible colonoscopy.
Participants undergo treatment in three parts, as follows:
- Part 1: Bortezomib alone: Patients receive 4 doses of bortezomib over 3 weeks. The drug is injected into a vein over about 30 seconds.
- Part 2: EPOCH-R chemotherapy plus bortezomib: This phase of treatment begins 3 to 4 weeks after completing Part 1. Treatment is given on an outpatient basis in six 3-week cycles, with all drugs administered over the first 5 days of each cycle. Patients take prednisone by mouth on days 1 to 5 and etoposide, doxorubicin, and vincristine as a 96-hour infusion through a vein over days 1 to 5. The infused drugs are delivered through a lightweight, portable infusion pump. Rituximab is given by vein over several hours on day 1 immediately before the chemotherapy infusion begins. Bortezomib is given by vein over 30 seconds on day 1 before the rituximab and again on day 4. Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the chemotherapy infusion is completed. Patients are taught how to self inject granulocyte colony stimulating factor (G-CSF), a drug that helps boost white cell counts after chemotherapy. They inject the drug under the skin (like an insulin shot) for 10 days of each cycle beginning day 6. Patients also take an antibiotic to help prevent infection during chemotherapy.
- Part 3: Bortezomib alone: After completing EPOCH-R-B therapy, patients are randomly assigned to receive or not to receive bortezomib alone. The drug is given in 2 doses over 5 days, with a break of 16 days before the next dose. These 3-week cycles continue for up to 18 months or until the disease comes back or worsens. Patients who are assigned to the group that does not receive bortezomib will be offered the drug if their disease relapses.
During therapy, patients have tests performed on their bone marrow, tumor tissue, blood or other fluids to look at different genes and proteins that may be involved in the development of their lymphoma or the reaction of the immune system. A tissue biopsy is done before treatment begins and a day after treatment starts. Disease progress is followed with computed tomography (CT) scans and blood tests. When treatment is completed, patients whose cancer has disappeared are scheduled for periodic follow-up examinations and tests. Those whose disease remains or recurs may be offered participation in another protocol if an appropriate one is available or are returned to the care of their local physician.
...
Detailed description
Background:
Mantle cell lymphoma (MCL) presents a clinical challenge because it is aggressive and incurable with chemotherapy. Therefore novel treatment approaches are needed.
MCL has overexpression of NF-kappa B (NF-kappa B), a transcription factor that affects cell growth and survival, and cyclin D1 that affects cell cycle and growth. These proteins appear to be involved in the pathogenesis of MCL.
Bortezomib, a proteasome inhibitor that inhibits NF-kappa B and cyclin D1, has demonstrated activity in patients with relapsed or refractory MCL.
Dose-adjusted-etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) has excellent activity in MCL, with a complete response (CR) rate of 92%, but patients eventually relapse.
Objective:
Determine the progression free survival (PFS) and overall survival (OS) of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab,bortezomib (DA-EPOCH-RB) followed by bortezomib maintenance versus observation.
Eligibility:
Diagnosis of mantle cell lymphoma.
No prior treatment except for local radiation or a short course of steroids for control of symptoms,
Age greater than or equal to 18 years old.
Adequate major organ function unless impairment is due to lymphoma.
Study Design:
To assess the clinical activity and biological effects of bortezomib, patients will initially receive one cycle of bortezomib alone with sequential tumor biopsies for microarray analysis.
All patients will then receive Dose-adjusted (DA)-EPOCH-RB for 6 cycles, and if they have at least a PR, this will be followed by randomization to either immediate bortezomib maintenance x 18 months, or to observation, followed by bortezomib if progression occurs. This study has as a primary goal, to describe progression free survival (PFS) and overall survival of early bortezomib maintenance versus observation following induction with bortezomib followed by DA-EPOCH-RB. Important secondary goals are to assess response and toxicity to bortezomib alone or DA-EPOCH-RB, to evaluate time to progression after receiving bortezomib following progression on an observation arm, and to assess the biological effects of bortezomib on untreated MCL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| EPOCH-R + Bortezomib | Experimental | Drug: Rituximab (R), Biological: EPOCH, Drug: BortezomibCombo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B) |
| Bortezomib "window" | Experimental | Drug: Bortezomib (B)Bortezomib alone |
| Bortezomib maintenance | Active comparator | Drug: BortezomibBortezomib maintenance |
| Observation | Other | Drug: Bortezomib or observationAt the beginning of part C patients are randomized to receive bortezomib maintenance or observation without bortezomib. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Rituximab (R)Also: RituxanRituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles. | Drug | EPOCH-R + Bortezomib |
| EPOCHEPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles. | Biological | EPOCH-R + Bortezomib |
| Bortezomib (B)Also: VelcadeBortezomib is given alone for one cycle. | Drug | Bortezomib "window" |
| BortezomibAlso: VelcadeBortezomib is given with EPOCH and rituximab every 6 weeks for 12 cycles. | Drug | Bortezomib maintenance, EPOCH-R + Bortezomib |
| Bortezomib or observationAlso: VelcadeAt the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib. | Drug | Observation |
Primary outcome
Progression Free Survival (PFS)
Time frame: up to 5 years
Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Median Overall Survival (OS)
Time frame: up to 9.9 years
Overall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Overall Progression Free Survival
Time frame: up to 9.9 years
Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.
Overall Survival
Time frame: up to 9.9 years
Overall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
2 secondary outcomes
Count of Participants With Serious and Non-Serious Adverse Events
Time frame: Date treatment consent signed to date off study, approximately 143 months and 7 days
Clinical Response
Time frame: up to 22 weeks after initiation of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8648383Velders GA, Kluin-Nelemans JC, De Boer CJ, Hermans J, Noordijk EM, Schuuring E, Kramer MH, Van Deijk WA, Rahder JB, Kluin PM, Van Krieken JH. Mantle-cell lymphoma: a population-based clinical study. J Clin Oncol. 1996 Apr;14(4):1269-74. doi: 10.1200/JCO.1996.14.4.1269.
- Background: PubMed 10319380Campo E, Raffeld M, Jaffe ES. Mantle-cell lymphoma. Semin Hematol. 1999 Apr;36(2):115-27.
- Background: PubMed 9586911Hiddemann W, Unterhalt M, Herrmann R, Woltjen HH, Kreuser ED, Trumper L, Reuss-Borst M, Terhardt-Kasten E, Busch M, Neubauer A, Kaiser U, Hanrath RD, Middeke H, Helm G, Freund M, Stein H, Tiemann M, Parwaresch R. Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol. 1998 May;16(5):1922-30. doi: 10.1200/JCO.1998.16.5.1922.
- Derived from this study: PubMed 35143622Lakhotia R, Melani C, Dunleavy K, Pittaluga S, Saba N, Lindenberg L, Mena E, Bergvall E, Lucas AN, Jacob A, Yusko E, Steinberg SM, Jaffe ES, Wiestner A, Wilson WH, Roschewski M. Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma. Blood Adv. 2022 Apr 26;6(8):2667-2680. doi: 10.1182/bloodadvances.2021006397.
- Derived from this study: PubMed 23940282Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, Kuil A, Herman SE, Chang S, Pals ST, Wilson W, Wiestner A, Spaargaren M, Buggy JJ, Elias L. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013 Oct 3;122(14):2412-24. doi: 10.1182/blood-2013-02-482125. Epub 2013 Aug 12.
- Derived from this study: PubMed 20956803Perez-Galan P, Mora-Jensen H, Weniger MA, Shaffer AL 3rd, Rizzatti EG, Chapman CM, Mo CC, Stennett LS, Rader C, Liu P, Raghavachari N, Stetler-Stevenson M, Yuan C, Pittaluga S, Maric I, Dunleavy KM, Wilson WH, Staudt LM, Wiestner A. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation. Blood. 2011 Jan 13;117(2):542-52. doi: 10.1182/blood-2010-02-269514. Epub 2010 Oct 18.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Wyndham H Wilson, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab (R), EPOCH and Bortezomib (B) in people with Lymphoma, Mantle Cell and Mantle Cell Lymphoma, run by National Cancer Institute (NCI) 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?
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 10 Oct 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression Free Survival (PFS) (time frame: up to 5 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00114738, which also lists 6 linked publications.
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 10 Oct 2022.