Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

University Hospital Plymouth NHS Trust

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Procedure: quality-of-life assessment; Drug: cyclophosphamide; Drug: bortezomib; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisolone; Other: questionnaire administration

Study type: Interventional

Funder types: Other

Identifiers

NCT00513955

CDR0000559820

EU-20747

ISRCTN200600609024

NCRN-Ply-26s

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bortezomib may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without bortezomib in treating mantle cell lymphoma.

PURPOSE: This randomized phase II trial is studying combination chemotherapy and bortezomib to see how well they work compared with combination chemotherapy alone in treating patients with relapsed or refractory mantle cell lymphoma. Combination chemotherapy alone (Arm I) has been discontinued April 2012 on recommendation of the DMC.

Full description

OBJECTIVES:

Primary

• To evaluate the rates of overall response (complete response [CR], CR unconfirmed [CRu], and partial response).

Secondary

• To evaluate the rates of CR and CRu.
• To determine the median time to progression.
• To determine the median overall survival.
• To evaluate the toxicity and tolerability.
• To compare the responses to these treatment regimens with those from first line therapy.
• To compare the quality of life.

OUTLINE: This is a randomized, open-label, parallel group, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (CHOP): Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Arm I has been discontinued April 2012 on recommendation of the DMC.
• Arm II (CHOP with bortezomib): Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5.

In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment.

After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of mantle cell lymphoma (MCL)

  • Expression of cyclin D1 or evidence of t(11;14) translocation by cytogenetics, FISH, or polymerase chain reaction

• Refractory to or relapsed or progressed after first line antineoplastic therapy

• Measurable disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2
• ANC ≥ 1,000/mm³ (not related to lymphoma)
• Platelet count ≥ 30,000/mm³
• AST and ALT ≤ 3 times upper limit of normal (ULN)
• Total bilirubin ≤ 2 times ULN
• Creatinine clearance ≥ 20 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria:

• Known serological positivity for HBV, HCV, or HIV
• History of allergic reaction attributable to compounds containing boron or mannitol
• Diagnosed or treated for a malignancy other than MCL within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or any in situ malignancy
• Active systemic infection requiring treatment
• Serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• Toxic effects of prior therapy or surgery must be resolved to ≤ grade 2

• Prior splenectomy or localized radiotherapy allowed

• Any prior chemotherapy regimen allowed

  • Chemotherapy may have been given in combination with rituximab

• Concurrent enrollment in a nontreatment study allowed, provided it does not interfere with participation in this study

Exclusion criteria:

• Prior bortezomib
• Antineoplastic therapy within the past 3 weeks
• Nitrosoureas within the past 6 weeks
• Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody within the past 4 weeks
• Radiotherapy within the past 3 weeks
• Major surgery within the past 2 weeks
• Concurrent investigational agents

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Bortezomib plus CHOP

Experimental group

Description:

Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.

Treatment:

Drug: bortezomib

Drug: cyclophosphamide

Drug: vincristine sulfate

Procedure: quality-of-life assessment

Drug: prednisolone

Drug: doxorubicin hydrochloride

Other: questionnaire administration