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

British Columbia Cancer Agency

Status and phase

Unknown

Phase 2

Conditions

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

Lymphoma, Non-Hodgkin

Treatments

Drug: Cyclophosphamide

Drug: Ondansetron

Drug: Mesna (IV)

Drug: Dexamethasone

Drug: Etoposide

Drug: Prednisone

Drug: Ifosfamide

Drug: Acetaminophen

Drug: Vincristine

Drug: Doxorubicin

Drug: Diphenhydramine

Other: PET Scan

Drug: Carboplatin

Drug: Rituximab

Drug: Mesna (oral)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00324467

H06-00017

Details and patient eligibility

About

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.

Full 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.

Enrollment

150 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

150 participants in 2 patient groups

R-CHOP (Negative Mid-Treatment PET Scan)

Active Comparator group

Description:

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.

Treatment:

Drug: Doxorubicin

Drug: Dexamethasone

Other: PET Scan

Drug: Diphenhydramine

Drug: Acetaminophen

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Diphenhydramine

Drug: Prednisone

Drug: Ondansetron

Drug: Acetaminophen

Drug: Dexamethasone

Drug: Ondansetron

R-ICE (Positive Mid-Treatment PET Scan

Active Comparator group

Description:

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.

Treatment:

Drug: Doxorubicin

Drug: Mesna (oral)

Drug: Mesna (IV)

Drug: Dexamethasone

Other: PET Scan

Drug: Diphenhydramine

Drug: Acetaminophen

Drug: Carboplatin

Drug: Vincristine

Drug: Rituximab

Drug: Cyclophosphamide