Clinical trial NCT00544219: PET Scans in Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
Official title: Prospective Evaluation of the Predictive Value of PET in Patients With Diffuse Large B-cell-lymphoma Under R-CHOP-14. A Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lymphoma
Keywords: contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2007-10-16
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Studying PET scans given to patients with cancer who are undergoing treatment may help doctors predict how patients will respond to treatment.

PURPOSE: This clinical trial is studying PET scans in patients with diffuse large B-cell lymphoma who are receiving rituximab together with cyclophosphamide, doxorubicin, vincristine, and prednisone.

Detailed description: OBJECTIVES:

Primary

* To evaluate if an early positive positron emission tomography (PET) scan after 2 courses of rituximab with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone can be used to identify a group of patients having a poor prognosis.

Secondary

* To compare modified PET/CT scan response criteria with revised standard response criteria.
* To evaluate, in a prospective manner, whether a proliferation-inducing ligand (APRIL) expression is a prognostic factor in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Rituximab IV alone is continued for an additional 2 courses after completion of the initial 6 courses.

Patients undergo positron emission tomography (PET) scan prior to and after completion of study therapy. Patients also undergo PET scan after course 2, and those with a positive PET result undergo an additional PET scan after course 4.

Previously collected tumor samples are analyzed for a proliferation-inducing ligand (APRIL) expression.

After completion of study treatment, patients are followed periodically for up to 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* Histologically confirmed diagnosis of CD20+ diffuse large B-cell lymphoma (DLBCL)

  * Stage I-IV disease
  * All IPI risk groups
* Must be positron emission tomography (PET)-positive
* At least one measurable lesion ≥ 15 mm in its shortest axis (greatest transverse diameter) for jugulodigastric and infra-carinal lymph nodes with CT scan (MRI is allowed only if CT scan cannot be performed)

  * Otherwise the shortest axis (greatest transverse diameter) must be ≥ 10 mm
  * Lesions should be selected according to the following features:

    * Clearly measurable in two perpendicular dimensions
    * From as disparate regions of the body as possible
    * Include mediastinal and retroperitoneal areas of disease whenever these sites are involved

Exclusion criteria:

* Secondary DLBCL (in transformation)
* Evidence of symptomatic CNS disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

* ECOG or WHO performance status 0-2
* Cardiac ejection fraction ≥ 50% as assessed by echocardiography
* Sufficient hematological values, hepatic and renal function
* Patient condition, compliance, and geographic proximity must allow proper staging and completion of treatment and follow-up
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 12 months after completion of study therapy

Exclusion criteria:

* Prior or concurrent hematological malignancies

  * Patients who have had prior solid organ tumors that required no treatment over the past 5 years and are currently disease-free are allowed
* Unstable cardiac disease within the past 6 months
* Any serious underlying medical condition (at the judgment of the investigator) that could impair the ability of the patient to participate in the study (e.g., active autoimmune disease, uncontrolled diabetes, HIV- and hepatitis-infection)
* Known hypersensitivity to any component of the study drugs

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

* Prior chemotherapy, radiotherapy, or immunotherapy (e.g., rituximab) for lymphoma
* Prior anthracycline treatment
* Concurrent radiotherapy
* Concurrent regular corticosteroids in the past 4 weeks

  * Doses ≤ 20 mg/day of prednisone for indications other than lymphoma or lymphoma-related symptoms allowed
* Concurrent drugs contraindicated for use with the study drugs according to the Swissmedic-approved product information
* Other concurrent experimental drugs or other anticancer therapy

Primary outcomes:
measure: Event-free survival
timeFrame: at 2 years
Secondary outcomes:
measure: Event-free survival
timeFrame: at 5 years
measure: Overall survival during follow-up
timeFrame: at 2 and 5 years
measure: Objective response
timeFrame: at 2 years
measure: Positron emission tomography (PET) results
timeFrame: at 2 years
measure: Histological results of remaining PET-positive lesion(s) after treatment
timeFrame: at 2 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: European Institute of Oncology
city: Aarau
country: Switzerland
facility: Hirslanden Klinik Aarau
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Baden
country: Switzerland
facility: Praxis Dr. Streit
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Rheinfelden
country: Switzerland
facility: Praxis Dr. Beretta
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Kantonsspital Aarau
name: Christoph Mamot, MD
role: STUDY_CHAIR
affiliation: Kantonsspital Aarau
name: Mario Bargetzi, MD
role: STUDY_CHAIR
affiliation: European Institute of Oncology
name: Giovanni Martinelli, MD
role: STUDY_CHAIR
References:
citation: Juskevicius D, Jucker D, Klingbiel D, Mamot C, Dirnhofer S, Tzankov A. Mutations of CREBBP and SOCS1 are independent prognostic factors in diffuse large B cell lymphoma: mutational analysis of the SAKK 38/07 prospective clinical trial cohort. J Hematol Oncol. 2017 Mar 17;10(1):70. doi: 10.1186/s13045-017-0438-7.
citation: Mamot C, Klingbiel D, Hitz F, Renner C, Pabst T, Driessen C, Mey U, Pless M, Bargetzi M, Krasniqi F, Gigli F, Hany T, Samarin A, Biaggi C, Rusterholz C, Dirnhofer S, Zucca E, Martinelli G. Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07). J Clin Oncol. 2015 Aug 10;33(23):2523-9. doi: 10.1200/JCO.2014.58.9846. Epub 2015 Jul 6.
citation: Tzankov A, Leu N, Muenst S, Juskevicius D, Klingbiel D, Mamot C, Dirnhofer S. Multiparameter analysis of homogeneously R-CHOP-treated diffuse large B cell lymphomas identifies CD5 and FOXP1 as relevant prognostic biomarkers: report of the prospective SAKK 38/07 study. J Hematol Oncol. 2015 Jun 14;8:70. doi: 10.1186/s13045-015-0168-7.
citation: Ceriani L, Gritti G, Cascione L, Pirosa MC, Polino A, Ruberto T, Stathis A, Bruno A, Moccia AA, Giovanella L, Hayoz S, Schar S, Dirnhofer S, Rambaldi A, Martinelli G, Mamot C, Zucca E. SAKK38/07 study: integration of baseline metabolic heterogeneity and metabolic tumor volume in DLBCL prognostic model. Blood Adv. 2020 Mar 24;4(6):1082-1092. doi: 10.1182/bloodadvances.2019001201.