Tailoring Treatment for B Cell Non-hodgkin's Lymphoma Based on PET Scan Results Mid Treatment

Summary

The purpose of this study is to assess whether patients who are likely to fail R-CHOP, as predicted by a mid-treatment PET scan, can have an improved outcome if switched to a standard salvage regimen R-ICE (rituximab, ifosfamide, carboplatin, etoposide).

Patients who have a negative PET scan after 4 cycles of R-CHOP have an excellent prognosis (\>85% chance of cure) and should complete treatment with 6 cycles of standard R-CHOP. Patients who have a positive PET scan after 4 cycles of R-CHOP have a very poor prognosis (\~10% chance of cure) and may have an improved outcome if switched to a non-cross resistant chemotherapy combination R-ICE.

Conditions

• Lymphoma, Non-Hodgkin
• Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Interventions

DRUG

Cyclophosphamide

Dose: 750 mg/m\^2 Administration: IV infusion day 1 over 20-60 minutes Schedule: Cycle 1, 2, 3, 4, 5\*, 6\* (Week 1, 4, 7, 10, 14, 17) \* Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan

DRUG

Doxorubicin

Dose: 50 mg/m\^2 Administration: IV Push day 1 Schedule: Cycle 1, 2, 3, 4, 5\*, 6\* (Week 1, 4, 7, 10, 14, 17) \* Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan

DRUG

Vincristine

Dose: 1.4 mg/m\^2 Administration: IV Push day 1 Schedule: Cycle 1, 2, 3, 4, 5\*, 6\* (Week 1, 4, 7, 10, 14, 17) \* Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan

DRUG

Prednisone

Dose: 45 mg/m\^2 Administration: IV infusion day 1 (or day 2) over 90 minutes-8 hours Schedule: Cycle 1, 2, 3, 4, 5\*, 6\* (Week 1, 4, 7, 10, 14, 17) \* Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan

DRUG

Ondansetron

Premedication for R-CHOP Dose: 8 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy

DRUG

Dexamethasone

Premedication for R-CHOP Dose: 12 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy

DRUG

Diphenhydramine

Premedication for R-CHOP Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion

DRUG

Acetaminophen

Premedication for R-CHOP Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion

DRUG

Ifosfamide

R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 5000 mg/m\^2 (total dose per cycle) Administration: In 3 equally divided doses IV infusion days 1,2,3, over 2 hours Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)

DRUG

Mesna (IV)

R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 5000 mg/m\^2 (total dose per cycle) Administration: In 3 equally divided doses IV infusion days 1,2,3 (with ifosfamide) over 2 hours Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)

DRUG

Mesna (oral)

R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 2 g Administration: PO 2h and 4h after ifosfamide infusion on days 1,2,3 Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)

DRUG

Carboplatin

R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 5 x (25+CrCl\*) (maximum dose 800 mg) Administration: IV infusion day 1 over 1 hour Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23) \*Carboplatin is dose via the Calvert formula with an AUC of 5, maximum dose 800 mg per cycle. Estimate Creatinine Clearance (CrCl)

DRUG

Etoposide

R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 100 mg/m\^2 Administration: IV infusion day 1,2,3 over 30 minutes Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)

DRUG

Rituximab

R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 375 mg/m\^2 Administration: IV infusion day 1 (or day 2 or day 3) over 90 minutes-8 hours Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)

DRUG

Ondansetron

Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily

DRUG

Dexamethasone

Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily

DRUG

Diphenhydramine

Premedication for R-ICE Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion

DRUG

Acetaminophen

Premedication for R-ICE Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion

OTHER

PET Scan

Investigations: 18F-FDG-PET scan Timing: After 4 cycles of R-CHOP (days 21-28) and after 4 cycles of R-ICE (days 28-35)

Sponsors & Collaborators

• Hoffmann-La Roche

  collaborator INDUSTRY

• British Columbia Cancer Agency

  lead OTHER

Principal Investigators

• Laurie H Sehn, MD · BC Cancer Agency - Vancouver Centre

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-08-31

Primary Completion

2021-12-31

Completion

2021-12-31

Countries

• Canada

Study Locations