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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT00324467
First received: May 9, 2006
Last updated: January 21, 2016
Last verified: January 2016
  Purpose

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.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma
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
Other: PET Scan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • Progression-free survival (PFS) in participants with advanced stage DLBCL [ Time Frame: Estimated two years ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Overall survival (OS) in participants with advanced stage DLBCL [ Time Frame: Several years ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 150
Study Start Date: August 2006
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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®
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
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.

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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324467

Locations
Canada, British Columbia
BC Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
British Columbia Cancer Agency
Hoffmann-La Roche
Investigators
Principal Investigator: Laurie H Sehn, MD BC Cancer Agency - Vancouver Centre
  More Information

Publications:
Jaffe ES, Harris NL, Stein H, Vardiman JW eds. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001.
Habermann TM, Weller EA, Morrison VA, et al. Phase III trial of Rituximab-CHOP (R-CHOP) vs. CHOP with a second randomization to maintenance rituximab (MR) or observation in patients 60 years of age and older with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;102:6 abstr.
Pfreundschuh M, Trumper L, Gill D, et al. First analysis of the completed Mabthera International (MInT) Trial in young patients with low-risk diffuse large B-cell lymphoma (DLBCL): Addition of rituximab to a CHOP-like regimen significantly improves outcome of all patients with the identification of a very favorable subgroup with IPI=0 and no bulky disease. Blood. 2004;104:48a.
Hutchings M, Mikhaeel NG, Fields P, Nunan T, O'Doherty M, Timothy A. The prognostic value of early FDG-PET during treatment of lymphoma and potential use in response-adapted treatment strategies. Annals of Oncology. 2005;16:280a.

Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT00324467     History of Changes
Other Study ID Numbers: H06-00017 
Study First Received: May 9, 2006
Last Updated: January 21, 2016
Health Authority: Canada: Health Canada

Keywords provided by British Columbia Cancer Agency:
NON-HODGKIN'S LYMPHOMA
POSITRON EMISSION TOMOGRAPHY
PET
DLBCL
R-CHOP
R-ICE

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Acetaminophen
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Diphenhydramine
Ifosfamide
Isophosphamide mustard
Mesna
Ondansetron
Prednisone
Promethazine
Rituximab
Vincristine
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, Local
Anti-Allergic Agents
Anti-Anxiety Agents

ClinicalTrials.gov processed this record on February 11, 2016