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

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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