PET Scans in Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

NCT ID: NCT00544219

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2016-01-31

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-Chop 14

Standard treatment

Group Type: OTHER

rituximab

Intervention Type: BIOLOGICAL

375 mg/m2 i.v. per cycle

cyclophosphamide

Intervention Type: DRUG

750 mg/m2 i.v. per cycle

doxorubicin hydrochloride

Intervention Type: DRUG

50 mg/m2 i.v. per cycle

prednisone

Intervention Type: DRUG

100 mg/day p.o. per cycle

vincristine sulfate

Intervention Type: DRUG

1.4 mg/m2 (max. 2.0 mg) i.v. per cycle

positron emission tomography

Intervention Type: PROCEDURE

PET Scan during treatment

Interventions

rituximab

375 mg/m2 i.v. per cycle

Intervention Type: BIOLOGICAL

cyclophosphamide

750 mg/m2 i.v. per cycle

Intervention Type: DRUG

doxorubicin hydrochloride

50 mg/m2 i.v. per cycle

Intervention Type: DRUG

prednisone

100 mg/day p.o. per cycle

Intervention Type: DRUG

vincristine sulfate

1.4 mg/m2 (max. 2.0 mg) i.v. per cycle

Intervention Type: DRUG

positron emission tomography

PET Scan during treatment

Intervention Type: PROCEDURE

Other Intervention Names

Mabthera; Endoxan; Adriamycin, Adriblastin; Deltasone, Orasone; Oncovin

Eligibility Criteria

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

• 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

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

PATIENT CHARACTERISTICS:

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Mamot, MD

Role: STUDY_CHAIR

Kantonsspital Aarau

Mario Bargetzi, MD

Role: STUDY_CHAIR

Kantonsspital Aarau

Giovanni Martinelli, MD

Role: STUDY_CHAIR

European Institute of Oncology

Locations

European Institute of Oncology

Milan, , Italy

Hirslanden Klinik Aarau

Aarau, , Switzerland

Kantonspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Praxis Dr. Streit

Baden, , Switzerland

Saint Claraspital AG

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Praxis Dr. Beretta

Rheinfelden, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Italy; Switzerland

References

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.

Reference Type: RESULT

PMID: 28302137 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26150440 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26071053 (View on PubMed)

Mendeville MS, Janssen J, Los-de Vries GT, van Dijk E, Richter J, Nijland M, Roemer MGM, Stathi P, Hijmering NJ, Bladergroen R, Pelaz DA, Diepstra A, Eertink CJ, Burggraaff CN, Kim Y, Lugtenburg PJ, van den Berg A, Tzankov A, Dirnhofer S, Duhrsen U, Huttmann A, Klapper W, Zijlstra JM, Ylstra B, de Jong D. Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma. Nat Commun. 2025 Jan 2;16(1):109. doi: 10.1038/s41467-024-55614-y.

Reference Type: DERIVED

PMID: 39747123 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32196557 (View on PubMed)

Other Identifiers

SWS-SAKK-38-07

Identifier Type: -

Identifier Source: secondary_id

EU-20763

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-001806-26

Identifier Type: -

Identifier Source: secondary_id

CDR0000569869

Identifier Type: -

Identifier Source: secondary_id

SAKK 38/07

Identifier Type: -

Identifier Source: org_study_id