Phase I/II Trial of VELCADE + CHOP-Rituximab in Untreated DLCBL or Mantle Cell NHL

Weill Cornell Medicine (WCM)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: Bortezomib, CHOP, Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00151320

0309006313

Details and patient eligibility

About

Primary Objective:

To determine the toxicity profile and maximum tolerated dose (MTD) of VELCADE when administered in combination with CHOP + Rituximab to patients with previously untreated diffuse large B cell or mantle cell non-Hodgkin's lymphoma (NHL)

Secondary Objectives:

To assess the response rate (overall and complete), event-free survival and overall survival with VELCADE and CHOP-R in patients with previously untreated diffuse large B cell or mantle cell lymphoma (phase II component)

Treatment:

Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles

Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications)

VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule:

Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4

Full description

Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles

Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications)

VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule:

Once completed six cycles of therapy (~18 weeks), patients will be evaluated every 3 months for the first year post treatment, then every 6 months until disease progression or death for years 2 through 5 post treatment. Patients who have disease progression will be contacted every 6 months until death to assess for survival status.

Enrollment: 76 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed diagnosis of diffuse large B cell or mantle cell Non-Hodgkin's Lymphoma with characteristic immunophenotypic profiles. For mantle cell: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-).
• Patient has not received any prior anti-cancer therapy for lymphoma
• Tumor tissue confirmed to express the CD20 antigen
• Available frozen tumor tissue(rebiopsy if needed)
• Patient has measurable disease as defined by a tumor mass > 1.5 cm
• Patient has Stage II, III, or IV disease
• Age > 18 years
• Absolute granulocyte count > 1000 cells/mm3
• Platelet count > 50,000 cells/mm3
• Creatinine < 2.0 x ULN
• Total bilirubin < 2.0 x ULN

Exclusion criteria

• Known central nervous system (CNS) involvement by lymphoma
• Known HIV disease
• Patient is pregnant or nursing
• Patient has had major surgery within the last 3 weeks
• Patient is receiving other investigational drugs
• Known peripheral neuropathy > Grade 2

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

76 participants in 1 patient group

Arm 1

Experimental group

Description:

Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by a dose escalation schedule.

Treatment:

Drug: Bortezomib, CHOP, Rituximab