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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma, Mantle Cell

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Trial Information

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


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

Objective:

Determine the PFS and OS of 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.

Inclusion Criteria


- ELIGIBILITY CRITERIA:

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).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival and overall survival 5 years after completion of study treatment

Safety Issue:

No

Principal Investigator

Wyndham H Wilson, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

050170

NCT ID:

NCT00114738

Start Date:

June 2005

Completion Date:

June 2013

Related Keywords:

  • Lymphoma, Mantle Cell
  • Proteasome Inhibition
  • NF-Kappa-B
  • Gene Expression Signature
  • Cyclin D1
  • Translational Studies
  • Lymphoma
  • Mantle Cell Lymphoma
  • MCL
  • Lymphoma
  • Lymphoma, Mantle-Cell

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892