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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00324467
Recruitment Status : Active, not recruiting
First Posted : May 11, 2006
Last Update Posted : July 22, 2021
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
British Columbia Cancer Agency

Tracking Information
First Submitted Date  ICMJE May 9, 2006
First Posted Date  ICMJE May 11, 2006
Last Update Posted Date July 22, 2021
Study Start Date  ICMJE August 2006
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2016)		 Progression-free survival (PFS) in participants with advanced stage DLBCL [ Time Frame: Estimated two years ]
Progression-free survival (PFS) in participants with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy. Progression-free survival is defined as the duration of time from diagnosis to time of disease progression or death from any cause. Living patients who have remained free of progression will have their PFS censored on the date last known alive.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
  • Overall survival (OS) in participants with advanced stage DLBCL [ Time Frame: Several years ]
    Overall survival (OS) in participants with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy. Overall survival will be defined as the time from diagnosis to the date of death. If the participant is lost to follow-up, survival will be censored on the last date the participant was known to be alive.
  • The safety of R-ICE therapy in first-line therapy of DLBCL following four cycles of R-CHOP as assessed using the NCI Common Terminology Criteria for Adverse Events Version 3.0 [ Time Frame: Six months ]
  • Investigate clinical and biologic markers that characterize participant heterogeneity and may serve as predictors of response to therapy and overall outcome. [ Time Frame: 1 year ]
    A central pathology review of original diagnostic biopsies will be performed by pathologists at the Coordinating Center to ensure appropriate lymphoma subclassification. This centralized review is not required prior to enrollment, provided the patients biopsy has been carefully reviewed by local pathologists and determined to be DLBCL. Correlative studies of biologic markers will be performed on cases with adequately preserved tissue to explore the biologic heterogeneity between patients and to investigate determinants of response to therapy.
  • Efficacy of tailoring first-line therapy bases on a mid-treatment PET scan result for patients with advanced stage DLBCL [ Time Frame: Four to six months ]
    All patients will have their BEST RESPONSE on study classified as outlined below. For patients with more than six measurable lesions the six most distinctly measurable at diagnosis should be chosen for response assessment by CT scanning. If available, lesions from both above and below the diaphragm should be chosen, at least two from each region.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tailoring Treatment for B Cell Non-hodgkin's Lymphoma Based on PET Scan Results Mid Treatment
Official Title  ICMJE Phase II Trial Investigating Tailoring First-Line Therapy For Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Mid-Treatment Positron Emission Tomography (PET) Scan Results
Brief 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.
Detailed Description

This is a phase II trial investigating tailoring first-line therapy for advanced stage diffuse large B-cell NHL (DLBCL) based on a mid-treatment 18F-FDG- positron-emission tomography (PET) scan result. More than half of all patients with DLBCL can be cured with 6-8 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Patients who are not cured with R-CHOP have a very poor prognosis. This study will 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).

Objectives:

  • To assess the efficacy of tailoring first-line therapy based on a mid- treatment PET scan result for patients with advanced stage DLBCL.
  • To assess the progression-free survival (PFS) in patients with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy.
  • To assess the overall survival (OS) in patients with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma, Non-Hodgkin
  • Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Intervention  ICMJE
  • 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

    Other Name: Cytoxan®, Neosar®
  • 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

    Other Name: Adriamycin ®, Rubex®
  • 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

    Other Name: Oncovin ®, Vincasar Pfs ®, Vincristine Sulfate, LCR, VCR
  • 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

    Other Name: Sterapred®, Sterapred® DS, Prednisone Intensol
  • Drug: Ondansetron
    Premedication for R-CHOP Dose: 8 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy
    Other Name: Zofran®, Zofran® ODT, Zuplenz®
  • Drug: Dexamethasone
    Premedication for R-CHOP Dose: 12 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy
    Other Name: Decadron®, Dexamethasone Intensol®, Dexpak® Taperpak®
  • Drug: Diphenhydramine
    Premedication for R-CHOP Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
    Other Name: Aler-Dryl®, Benadryl®, Nytol®, Diphenhist®
  • Drug: Acetaminophen
    Premedication for R-CHOP Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
    Other Name: Tylenol®
  • 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)
    Other Name: Ifex®, Isophosphamide
  • 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)
    Other Name: Mesnex®, Sodium 2-mercaptoethanesulfonate
  • 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)
    Other Name: Mesnex®, Sodium 2-mercaptoethanesulfonate
  • 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)

    Other Name: CBDCA
  • 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)
    Other Name: Etopophos®, VP-16
  • 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)
    Other Name: Rituxan®
  • Drug: Ondansetron
    Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily
    Other Name: Zofran®, Zofran® ODT, Zuplenz®
  • Drug: Dexamethasone
    Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily
    Other Name: Decadron®, Dexamethasone Intensol®, Dexpak® Taperpak®
  • Drug: Diphenhydramine
    Premedication for R-ICE Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
    Other Name: Aler-Dryl®, Benadryl®, Nytol®, Diphenhist®
  • Drug: Acetaminophen
    Premedication for R-ICE Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
    Other Name: Tylenol®
  • 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)
    Other Name: Positron emission tomography (PET) scan
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone
    • Drug: Ondansetron
    • Drug: Dexamethasone
    • Drug: Diphenhydramine
    • Drug: Acetaminophen
    • Other: PET Scan
  • 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.

    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone
    • Drug: Ondansetron
    • Drug: Dexamethasone
    • Drug: Diphenhydramine
    • Drug: Acetaminophen
    • Drug: Ifosfamide
    • Drug: Mesna (IV)
    • Drug: Mesna (oral)
    • Drug: Carboplatin
    • Drug: Etoposide
    • Drug: Rituximab
    • Drug: Ondansetron
    • Drug: Dexamethasone
    • Drug: Diphenhydramine
    • Drug: Acetaminophen
    • Other: PET Scan
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 9, 2006)		 150
Original Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 years of age or older
  • newly diagnosed histologically proven CD-20 positive diffuse large B- cell lymphoma by tissue biopsy, listed under peripheral B-cell neoplasm according to the WHO/REAL classification (diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, T-cell rich B-cell lymphoma, intravascular large B-cell lymphoma)
  • Advanced stage disease defined as - patients with stage III or stage IV disease; or patients with stage I or stage II disease with one of the following additional criteria: B-symptoms, or disease that is not radio- encompassable within a single involved field, or not a candidate for brief chemotherapy and irradiation, or the presence of bulky disease (any single mass => 10 cm)
  • Previously untreated or treated with up to 3 cycles of standard dose 3- weekly R-CHOP chemotherapy prior to enrollment (i.e. patients may be enrolled prior to initiation of the fourth cycle of R-CHOP chemotherapy)
  • ECOG Performance Status 0,1 or 2 at time of enrollment
  • No evidence of progressive disease while on R-CHOP chemotherapy
  • The patient must sign the consent form prior to registration

Exclusion Criteria:

  • Patients with a history of any other lymphoproliferative disorder, including prior history of indolent NHL
  • Patients with a history of prior or concurrent malignancies within 5 years of the current diagnosis, except adequately treated non- melanoma skin cancer, and curatively treated in-situ cancer of the cervix
  • Known HIV infection
  • Known hepatitis B virus infection
  • Pregnancy or lactation. Men and women of childbearing age must be using adequate contraception.
  • Significant renal insufficiency (serum creatinine > 200 mmol/L), unless due to lymphoma
  • Significant hepatic insufficiency (serum total bilirubin > 30 mmol/L), unless due to lymphoma
  • Cardiac contraindication to doxorubicin therapy (e.g. abnormal contractility on echocardiography). If history of cardiac disease, ejection fraction must be within normal limits for age.
  • Neurologic contraindication to vincristine (e.g. peripheral neuropathy)
  • Absolute neutrophil count <1.5 x 109/L (unless due to bone marrow involvement with lymphoma or due to initiation of R-CHOP chemotherapy)
  • Platelet count < 100 x 109/L (unless due to splenomegaly, bone marrow involvement with lymphoma or due to initiation of R-CHOP chemotherapy)
  • Evidence of active systemic infection
  • Any medical condition that in the opinion of the investigator would compromise treatment delivery, add toxicity or impair assessment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00324467
Other Study ID Numbers  ICMJE H06-00017
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party British Columbia Cancer Agency
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE British Columbia Cancer Agency
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Principal Investigator: Laurie H Sehn, MD BC Cancer Agency - Vancouver Centre
PRS Account British Columbia Cancer Agency
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP