EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00114738
Recruitment Status : Active, not recruiting
First Posted : June 17, 2005
Last Update Posted : January 2, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

This study will evaluate the effectiveness of 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, 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 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 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.

Condition or disease Intervention/treatment Phase
Lymphoma, Mantle Cell Mantle Cell Lymphoma Drug: Rituximab (R) Biological: EPOCH Drug: Bortezomib (B) Drug: Bortezomib Drug: Bortezomib or observation Phase 2

Detailed Description:


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-EPOCH-R has excellent activity in MCL, with a complete response (CR) rate of 92%, but patients eventually relapse.


Determine the PFS and OS of DA-EPOCH-RB followed by bortezomib maintenance versus observation.


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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 15, 2005
Actual Primary Completion Date : August 11, 2016
Estimated Study Completion Date : August 11, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Bortezomib

Arm Intervention/treatment
Experimental: B
Combo chemo EPOCH-R + B
Drug: Rituximab (R)
Rituximab is given with EPOCH and bortezomib every 3 weeks for 6 cycles.

Biological: EPOCH
EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.

Drug: Bortezomib (B)
Bortezomib is given alone for one cycle.

Experimental: A
Bortezomib alone
Drug: Bortezomib (B)
Bortezomib is given alone for one cycle.

Drug: Bortezomib or observation
At the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib.

Active Comparator: C
Bortezomib maintenance
Drug: Bortezomib
Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.

Primary Outcome Measures :
  1. PFS and OS [ Time Frame: Time of progression and death ]
    The primary evaluation will be a Kaplan-Meier analysis with a twotailed log rank test.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Diagnosis of mantle cell lymphoma (confirmed at 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.

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; 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 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.

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-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 FDG scan is anyone exceeding the weight limit of the scanner (350 lb).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00114738

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00114738     History of Changes
Obsolete Identifiers: NCT00131976
Other Study ID Numbers: 050170
First Posted: June 17, 2005    Key Record Dates
Last Update Posted: January 2, 2018
Last Verified: December 9, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Proteasome Inhibition
Gene Expression Signature
Cyclin D1
Translational Studies
Mantle Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents