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

Sponsor
British Columbia Cancer Agency
Study ID
NCT00324467
Phase
PHASE2
Status
Unknown

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Cyclophosphamide — DRUG
    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
  • Doxorubicin — DRUG
    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
  • Vincristine — DRUG
    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
  • Prednisone — DRUG
    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
  • Ondansetron — DRUG
    Premedication for R-CHOP Dose: 8 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy
  • Dexamethasone — DRUG
    Premedication for R-CHOP Dose: 12 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy
  • Diphenhydramine — DRUG
    Premedication for R-CHOP Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
  • Acetaminophen — DRUG
    Premedication for R-CHOP Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
  • Ifosfamide — DRUG
    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)
  • Mesna (IV) — DRUG
    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)
  • Mesna (oral) — DRUG
    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)
  • Carboplatin — DRUG
    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)
  • Etoposide — DRUG
    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)
  • Rituximab — DRUG
    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)
  • Ondansetron — DRUG
    Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily
  • Dexamethasone — DRUG
    Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily
  • Diphenhydramine — DRUG
    Premedication for R-ICE Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
  • Acetaminophen — DRUG
    Premedication for R-ICE Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
  • PET Scan — OTHER
    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)

Study Details

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.

Key Dates

First listed
May 11, 2006
Start date
Aug 31, 2006
Status verified
Jul 2021
Primary completion
Dec 31, 2021
Completion
Dec 31, 2021

Study Design

Enrollment
150 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Active Comparator: R-CHOP (Negative Mid-Treatment PET Scan)
    All participants will receive 4 cycles of standard dose R-CHOP chemotherapy administered at 3-weekly intervals. Non-progressing participants will undergo a mid-treatment PET scan along with routine restaging investigations after 4 cycles of R-CHOP. Patients with a negative mid-treatment PET scan (no evidence of abnormal 18F-FDG uptake) will complete therapy with two additional cycles of R-CHOP for a total of 6 cycles of chemotherapy. Patients with a mid-treatment PET scan interpreted to be "indeterminate" or "equivocal" will be recorded as such, but should be considered negative for the purpose of treatment planning and should not prompt a change in therapy.
  • Active Comparator: R-ICE (Positive Mid-Treatment PET Scan
    All participants will receive 4 cycles of standard dose R-CHOP chemotherapy administered at 3-weekly intervals. Non-progressing participants will undergo a mid-treatment PET scan along with routine restaging investigations after 4 cycles of R-CHOP. Patients with a mid-treatment PET scan (abnormal 18F-FDG uptake) will be switched to R-ICE chemotherapy and receive 4 cycles of R-ICE for a total of 8 cycles of chemotherapy. Following completion of R-ICE chemotherapy, patients will undergo a post-treatment PET scan along with routine restaging investigations. The post-treatment PET scan will be performed between days 28 and 35 following the final cycle of R-ICE. Patients with a negative post-treatment PET scan will undergo no further therapy. Patients with a positive post-treatment PET scan corresponding to persistent abnormalities on CT scan will be considered for radiation therapy to PET positive sites.

Primary Outcome Measure

Progression-free survival (PFS) in participants with advanced stage DLBCL [ Time Frame: Estimated two years ]

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