Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Bortezomib, Rituximab, and Combination Chemotherapy in Treating Patients With Mantle Cell Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over NCI NCI-05-C-0170 NCI-6450, NCT00131976

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

1. Compare the progression-free and overall survival of patients with previously untreated mantle cell lymphoma treated with single-agent bortezomib followed by dose-adjusted induction therapy comprising bortezomib in combination with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) and maintenance therapy comprising bortezomib vs observation.

Secondary

1. Determine the response in patients treated with single-agent bortezomib administered before dose-adjusted induction therapy.
2. Determine toxicity of dose-adjusted induction therapy in these patients.
3. Determine the response in patients treated with dose-adjusted induction therapy.
4. Determine the response and progression-free survival of patients initially randomized to the observation arm who are subsequently treated with bortezomib at the onset of disease progression.
5. Compare the time to non-protocol treatment in patients treated with maintenance therapy comprising bortezomib vs observation.
6. Correlate microarray and proteomic findings with clinical outcome of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Diagnosis of mantle cell lymphoma
  • All stages and variants allowed



• No known CNS lymphoma

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Prior short course of steroids for control of symptoms allowed

Radiotherapy

• Prior local radiotherapy for control of symptoms allowed

Surgery

• Not specified

Other

• No other prior treatment for mantle cell lymphoma

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3*
• Platelet count > 75,000/mm^3*

 [Note: *Unless impairment is due to organ involvement by lymphoma]

Hepatic

• Bilirubin < 2 mg/dL (5mg/dL in patients with Gilbert's syndrome, defined as > 80% unconjugated bilirubin)*

 [Note: *Unless impairment is due to organ involvement by lymphoma]

Renal

• Creatinine ≤ 1.5 mg/dL*

  OR

• Creatinine clearance > 50 mL/min*

 [Note: *Unless impairment is due to organ involvement by lymphoma]

Cardiovascular

• No active symptomatic ischemic heart disease

 [Note: *Patients with a history of myocardial infarction or congestive heart failure must undergo MUGA or echocardiogram]

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other invasive malignancy within the past 5 years
• No peripheral neuropathy ≥ grade 2
• No history of hypersensitivity to boron or mannitol

Expected Enrollment

A total of 80 patients (40 per maintenance treatment arm) will be accrued for this study within 2 years.

Outcomes

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

Response at the end of dose-adjusted induction therapy
Response and toxicity at the end of maintenance therapy
Response and progression-free survival of bortezomib at disease progression in the observation treatment arm 5 years after completion of study treatment
Time to non-protocol treatment in the maintenance and observation treatment arms 5 years after completion of study treatment
Correlation of mircoarray and proteomic findings with clinical outcomes as measured by cDNA microarray 5 years after completion of study treatment

Outline

This is a randomized study.

• Single-agent bortezomib: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11.



• Dose-adjusted induction therapy: Beginning within 22-28 days after the start of single-agent bortezomib, patients receive rituximab IV on day 1 followed by etoposide, doxorubicin, and vincristine IV continuously over 96 hours on days 1-4. Patients also receive bortezomib IV over 3-5 seconds on days 1 and 4; oral prednisone twice daily on days 1-5; and cyclophosphamide IV over 15 minutes on day 5. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until day 15 or until blood counts recover. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.



• Maintenance therapy: Patients who achieve at least a partial response to dose-adjusted induction therapy are randomized to 1 of 2 arms.
  • Arm I: Beginning 8-12 weeks after the completion of dose-adjusted induction therapy, patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 8 weeks for up to 18 months in the absence of disease progression or unacceptable toxicity.
  
  
  
  • Arm II: Patients undergo observation only. Patients with disease progression receive bortezomib as in arm I. Treatment repeats every 4 weeks for up to 18 months.
  
  
  

After completion of study treatment, patients are followed every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Wyndham Wilson, MD, PhD, Principal investigator		Ph: 301-435-2415 Email: wilsonw@mail.nih.gov

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research
		Therese White, RN	Ph:  301-402-5886
			Email: whiteth@mail.nih.gov
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Featured trial article
Web site for additional information

Registry Information
Official Title		Randomized Phase II Study of Dose-Adjusted Epoch-Rituximab-Bortezomib Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics
Trial Start Date		2005-06-22
Trial Completion Date		2013-06-22 (estimated)
Registered in ClinicalTrials.gov		NCT00131976
Date Submitted to PDQ		2005-06-22
Information Last Verified		2008-11-30

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