The Palliative Benefit of Involved-site Radiotherapy for Patients With Advanced-stage Diffuse Large B-cell Lymphoma

NCT ID: NCT02449278

Last Updated: 2015-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2025-10-31

Brief Summary

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The standard treatment approach for patients with stage III-IV DLBCL is combination chemotherapy. Receipt of consolidation radiotherapy (RT) after effective chemotherapy was associated with improved in-field control and event-free survival. However, it is uncertain for the radiotherapy field size to treat for these patients after chemotherapy. Involved-field radiotherapy (IFRT) after effective chemotherapy is a common strategy for patients with stage III-IV DLBCL. There is not a clinical trial to research whether the sequential narrowed radiotherapy field size (involved-site radiotherapy, ISRT) can obtain the same efficacy as IFRT and decrease toxicities related to radiotherapy.

Detailed Description

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Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Approximately 50% of patients present with stage III-IV disease at diagnosis. The standard treatment approach for these patients is combination chemotherapy. the role of radiation therapy (RT) after effective system therapy in stage III-IV DLBCL (advanced-stage DLBCL) is controversial. The recommended approaches for patients with stage III-IV disease by The National Comprehensive Cancer Network (NCCN) are that consolidation RT is managed for patients who achieved a complete response (CR) to chemotherapy and palliative RT for patients with partial response (PR) after chemotherapy. However, it is uncertain for the radiotherapy field size to treat for these patients after chemotherapy.

Some benefits of consolidation RT after chemotherapy exist for patients with advanced-stage DLBCL. One of the important aims of treatment for these patients is the improvement of event-free survival (EFS). After patients receive chemotherapy alone, the most common site of disease recurrence is at sites of initial disease involvement. The complications related to chemotherapy, including second malignancies and other non-neoplastic late events, were needed to emphasize for those patients managed with more cycles' regimens alone to increase the efficacy of patients with advanced-stage DLBCL. Receipt of consolidation RT was associated with improved in-field control and EFS though no difference in overall survival (OS) when compared to patients without consolidation RT. Several randomized and retrospective studies demonstrated that the EFS (even the OS) can be improved by consolidation RT for patients with advanced-stage DLBCL after CHOP or CHOP-like chemotherapy. The patients randomized among those diagnosed initially with bulky disease (\>10 cm), those achieving CR or PR after chemotherapy, and even those in stage IV with bone marrow involved.

The complications related to consolidation RT also need to be additionally explored for those patients since the efficacy of advanced-stage DLBCL has improved by combined-modality therapy (CMT). Especially, considerable difficulties in the continuous salvage options are unavoidable because of the risk of blood cell production disorders associated to extensive-field radiotherapy. Consolidation involved-field radiotherapy (IFRT) after effective chemotherapy is common palliative strategy for patients with advanced-stage DLBCL. The morbidity of treatment may be decreased further by RT with the radiation field size reduction. Involved-site radiotherapy (ISRT), based on a modified involved field, aims to reduce the radiation volume treated and the probability of late effects. Its radiation targets include a gross tumor volume (GTV), a clinical target volume (CTV), and a planning target volume (PTV), which were defined in International Commission on Radiation Units and Measurements Report (ICRU) 50. This is based on defining the site of gross disease before chemotherapy, the GTV and using a CT-based volume with an expansion to form a CTV in the cranio-caudal direction. There is not a clinical trial to research whether the sequential narrowed radiotherapy field size (involved-site radiotherapy, ISRT) can obtain the same efficacy as IFRT and decrease toxicities related to radiotherapy.

To evaluate the differences between IFRT and ISRT in the efficacy and complications related to consolidation RT for patients with advanced-stage DLBCL who achieved effective chemotherapy. The CTV of ISRT is defined as the region including the prechemotherapy volume of disease with 1.5 cm margin expanded cranio-caudally in the direction of potential lymphatic spread. The CTV should not extend into air in the transverse plane and should be limited in the involved lymph node region defined by the Cancer and Leukemia Group B (CALGB). The PTV is then extended from CTV by adding the necessary margin for setup error and organ motion.

Conditions

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Diffuse Large B-cell Lymphoma

Keywords

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advanced-stage DLBCL ISRT chemotherapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ISRT group

Six cycles Chemotherapy (cyclophosphamide 750mg/square meter on day 1 + doxorubicin 50mg/square meter on day 1 + vincristine 1.4mg/square meter on day 1 (up to a maximal dose of 2 mg) + prednisone 60mg/square meter on day 1 through 5, repeated at 21-day intervals) .

Consolidation involved-site radiotherapy (ISRT) following in patient with complete or partial response beginning 1 month after last cycle of chemotherapy.

Group Type EXPERIMENTAL

Consolidation involved-site radiotherapy (ISRT)

Intervention Type RADIATION

6 cycles modern CHOP chemotherapy followed consolidation involved-site radiotherapy (ISRT).

Involved-site radiotherapy (ISRT) is based on defining the site of gross disease before chemotherapy, the GTV and using a CT-based volume with an expansion to form a CTV in the cranio-caudal direction.

The general dose had been guided that 30-36Gy in 15\~18 fractions of 2 Gy 5 days per week was managed for patients with complete response (CR) after chemotherapy and 40-50Gy in 20\~25 fractions of 2 Gy 5 days per week for partial response (PR).

cyclophosphamide

Intervention Type DRUG

Patients in both arms will be given cyclophosphamide chemotherapy

doxorubicin

Intervention Type DRUG

Patients in both arms will be given doxorubicin chemotherapy

vincristine

Intervention Type DRUG

Patients in both arms will be given vincristine chemotherapy

prednisone

Intervention Type DRUG

Patients in both arms will be given prednisone chemotherapy

IFRT group

Six cycles Chemotherapy (cyclophosphamide 750mg/square meter on day 1 + doxorubicin 50mg/square meter on day 1 + vincristine 1.4mg/square meter on day 1 (up to a maximal dose of 2 mg) + prednisone 60mg/square meter on day 1 through 5, repeated at 21-day intervals).

Consolidation involved-field radiotherapy (IFRT) following in patient with complete or partial response beginning 1 month after last cycle of chemotherapy.

Group Type ACTIVE_COMPARATOR

Consolidation involved-field radiotherapy (IFRT)

Intervention Type RADIATION

6 cycles modern CHOP chemotherapy followed consolidation involved-field radiotherapy (IFRT).

Radiotherapy field of IFRT defined by CALGB is encompassed the prechemotherapy gross tumor.

The general dose had been guided that 30-36Gy in 15\~18 fractions of 2 Gy 5 days per week was managed for patients with complete response (CR) after chemotherapy and 40-50Gy in 20\~25 fractions of 2 Gy 5 days per week for partial response (PR).

cyclophosphamide

Intervention Type DRUG

Patients in both arms will be given cyclophosphamide chemotherapy

doxorubicin

Intervention Type DRUG

Patients in both arms will be given doxorubicin chemotherapy

vincristine

Intervention Type DRUG

Patients in both arms will be given vincristine chemotherapy

prednisone

Intervention Type DRUG

Patients in both arms will be given prednisone chemotherapy

Interventions

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Consolidation involved-site radiotherapy (ISRT)

6 cycles modern CHOP chemotherapy followed consolidation involved-site radiotherapy (ISRT).

Involved-site radiotherapy (ISRT) is based on defining the site of gross disease before chemotherapy, the GTV and using a CT-based volume with an expansion to form a CTV in the cranio-caudal direction.

The general dose had been guided that 30-36Gy in 15\~18 fractions of 2 Gy 5 days per week was managed for patients with complete response (CR) after chemotherapy and 40-50Gy in 20\~25 fractions of 2 Gy 5 days per week for partial response (PR).

Intervention Type RADIATION

Consolidation involved-field radiotherapy (IFRT)

6 cycles modern CHOP chemotherapy followed consolidation involved-field radiotherapy (IFRT).

Radiotherapy field of IFRT defined by CALGB is encompassed the prechemotherapy gross tumor.

The general dose had been guided that 30-36Gy in 15\~18 fractions of 2 Gy 5 days per week was managed for patients with complete response (CR) after chemotherapy and 40-50Gy in 20\~25 fractions of 2 Gy 5 days per week for partial response (PR).

Intervention Type RADIATION

cyclophosphamide

Patients in both arms will be given cyclophosphamide chemotherapy

Intervention Type DRUG

doxorubicin

Patients in both arms will be given doxorubicin chemotherapy

Intervention Type DRUG

vincristine

Patients in both arms will be given vincristine chemotherapy

Intervention Type DRUG

prednisone

Patients in both arms will be given prednisone chemotherapy

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Both male and female aged range from 18 years to 65 years.
* Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1.
* All patients had histologically confirmed Diffuse large B-cell lymphoma.
* Advanced-stage DLBCL patients at newly diagnosed or recurrent without RT in initial management.
* Adequate organ function.
* Negative pregnancy test.
* Signed informed consent document on file.

Exclusion Criteria

* Woman who were pregnant or lactating.
* With severe local infection or general infective disease.
* Primary lymphoma in special organ including cuticula, center never system, gastrointestinal tract, testicle, and lung.
* With other second primary malignancy except cutaneum carcinoma.
* Being or planning to participate in other study.
* Any patient who in the opinion of the investigator should not participate in the study.

Withdrawal Criteria:

* Patient are free to withdrawal completely from the study at any time upon request.
* Patient in the study may be stopped with the patient agreement at any time at the discretion of investigator.
* In-field progression on irradiation ongoing.
* Poor tolerability adverse events in the period of chemotherapy or irradiation after enrolled in the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wuhan University

OTHER

Sponsor Role lead

Responsible Party

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Di Deng

Director,Clinical Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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DiDeng

Wuhan, Hubei, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Di Deng, MD

Role: CONTACT

Phone: 0086-27-67813153

Email: [email protected]

Wei Du, MD

Role: CONTACT

Phone: 0086-18972161688

Email: [email protected]

Other Identifiers

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WUCC-NHL04 Trial

Identifier Type: -

Identifier Source: org_study_id