R-MegaCHOP-ESHAP-BEAM in Patients With High-Risk Aggressive B-Cell Lymphomas

NCT ID: NCT00558220

Last Updated: 2007-11-14

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

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-05-31

Study Completion Date

2006-10-31

Brief Summary

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The purpose of this study is to show if addition of Rituximab to intensive induction (MegaCHOP/ESHAP) and high-dose consolidation (BEAM) improves progression-free and overall survival in patients younger than 65 years with aggressive B-cell lymphoma and aaIPI 2 or 3.

Detailed Description

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Previous study of Czech Lymphoma Study Group (4\_2002)have shown that intensive induction (MegaCHOP - Cyclophosphamide 3 g/m2, Vincristine 2 mg, Adriamycin 75 mg/m2, Prednisone 300 mg/m2 every three weeks with G-CSF for three cycles, followed by ESHAP - Etoposide 240 mg/m2, Cisplatin 100 mg/m2, Solumedrol 2000 mg and cytarabine 2000 mg/m2 for three cycles every three weeks with G-CSF) followed by intensive consolidation (BEAM) and stem cell support improves progression-free survival in adult patients (18-65 years old) with aggressive B-cell lymphoma (namely, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and follicular lymphoma grade II) with aaIPI 2 and namely, with aaIPI 3. This study was aimed to find out if addition of four to six doses of Rituximab 375 mg/m2 on first day of every cycle of intensive induction further improves prognosis of these patients.

Inclusion criteria for this trial were:

* newly diagnosed aggressive B-cell lymphoma, namely diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and follicular lymphoma grade III
* age 18-65 years
* age adjusted IPI (International Prognostic Index) score 2 or 3
* ECOG performance status 0-3
* signed informed consent

Exclusion criteria were:

* relapsed lymphoma
* previous treatment (up to one cycle of standard pretreatment - COP, CHOP or steroids was permitted and later became mandatory to decrease disease burden and/or improve the performance status of the patient)
* Burkitt lymphoma
* posttransplant lymphoproliferation
* CNS involvement
* other malignant tumor in previous history, except basalioma, skin squamocellular carcinoma or cervical carcinoma in situ
* other serious comorbidity

Primary endpoints was progression-free survival

Secondary endpoints were:

* rate of complete remission and overall response rate
* overall survival
* toxicity of the protocol, measured as grade III-IV toxicity and/or inability to finish the protocol as planned

Planned number of accrued patients was 100.

Conditions

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Diffuse Large B-Cell Lymphoma. Primary Mediastinal B-Cell Lymphoma Follicular Lymphoma Grade III

Keywords

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Lymphoma, B-cell Immunotherapy, passive Remission induction Autologous transplantation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

Intensive induction followed by high-dose consolidation with stem cell support ± radiotherapy

Group Type EXPERIMENTAL

immunotherapy

Intervention Type PROCEDURE

Given together with induction chemotherapy:

Rituximab - 375 mg/m2 iv every 3 weeks, 4-6 doses

Induction treatment part 1

Intervention Type PROCEDURE

cyclophosphamide 3000 mg/m2 iv every 3 weeks, 3 cycles vincristin 2 mg iv every 3 weeks, 3 cycles doxorubicin 75 mg/m2 iv every 3 weeks, 3 cycles Prednisolone 300 mg/m2 divided into five days po every 3 weeks, 3 cycles pegfilgrastim 6 mg sc every 3 weeks.

3 cycles consisting of combination treatment of above mentioned drugs are given.

Induction treatment part 2 with PBPC collection

Intervention Type PROCEDURE

Starts three weeks after last cycle of Induction part 1.

Etoposide 240 mg/m2 divided into equal doses for four days, together with methylprednisolone 2000 mg divided into equal doses for four days, together with cisplatin 100 mg/m2 divided into equal doses for four days, and together with cytarabine 2000 mg/m2 iv one dose on 4th day of treatment. Filgrastim 10-12 ug/kg from day five after start of chemotherapy untill stem cell collection.

Peripheral blood progenitor cell collection (PBPC) is started when CD34 positive cells are \>20/cubic milimeter of blood and continued untill 5 million of CD34 positive cells are collected from peripheral blood.

Induction treatment part 3

Intervention Type PROCEDURE

Part 3 of induction treatment is given approximately one week after the end of Part 2.

Etoposide 240 mg/m2 divided into equal doses for four days, methylprednisolone 2000 mg divided into equal doses for four days, cisplatin 100 mg/m2 divided into equal doses for four days, cytarabine 2000 mg/m2 iv one dose on day 4 of chemotherapy and pegfilgrastim 6 mg on day five of chemotherapy are given twice three weeks apart.

Consolidation treatment part 1: HD-chemotherapy with ASCT

Intervention Type PROCEDURE

Consolidation treatment Part 1 starts 4-8 weeks after the second cycle of Induction treatment Part 3.

High dose chemotherapy (HD-chemotherapy) consists of:

BCNU 300 mg/m2 is given on day 1, etoposide 800 mg/m2 divided into four equal doses is given on day 2-5, cytarabine 1600 mg/m2 divided into eight equal doses is given on day 2-5, melphalan 140 mg/m2 is given on day 6.

On day 7, collected stem cells from peripheral blood (see Induction treatment part 1) are infused back to the patient. This is called autologous transplantation (ASCT). Filgrastim 5 ug/kg is given from day 14 (start of the chemotherapy being day 1) until neutrophil recovery.

Consolidation treatment part 2: Radiotherapy

Intervention Type RADIATION

Radiotherapy is started given 4-8 weeks after the autologous transplantation. It is given to patients with initially bulky disease (\>10 cm at diagnosis) or to patients with residual disease after Induction treatment part 1-3 and Consolidation treatment part 1. 30-40 Gy are given in 2 Gy fractions over 3-4 weeks.

Interventions

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immunotherapy

Given together with induction chemotherapy:

Rituximab - 375 mg/m2 iv every 3 weeks, 4-6 doses

Intervention Type PROCEDURE

Induction treatment part 1

cyclophosphamide 3000 mg/m2 iv every 3 weeks, 3 cycles vincristin 2 mg iv every 3 weeks, 3 cycles doxorubicin 75 mg/m2 iv every 3 weeks, 3 cycles Prednisolone 300 mg/m2 divided into five days po every 3 weeks, 3 cycles pegfilgrastim 6 mg sc every 3 weeks.

3 cycles consisting of combination treatment of above mentioned drugs are given.

Intervention Type PROCEDURE

Induction treatment part 2 with PBPC collection

Starts three weeks after last cycle of Induction part 1.

Etoposide 240 mg/m2 divided into equal doses for four days, together with methylprednisolone 2000 mg divided into equal doses for four days, together with cisplatin 100 mg/m2 divided into equal doses for four days, and together with cytarabine 2000 mg/m2 iv one dose on 4th day of treatment. Filgrastim 10-12 ug/kg from day five after start of chemotherapy untill stem cell collection.

Peripheral blood progenitor cell collection (PBPC) is started when CD34 positive cells are \>20/cubic milimeter of blood and continued untill 5 million of CD34 positive cells are collected from peripheral blood.

Intervention Type PROCEDURE

Induction treatment part 3

Part 3 of induction treatment is given approximately one week after the end of Part 2.

Etoposide 240 mg/m2 divided into equal doses for four days, methylprednisolone 2000 mg divided into equal doses for four days, cisplatin 100 mg/m2 divided into equal doses for four days, cytarabine 2000 mg/m2 iv one dose on day 4 of chemotherapy and pegfilgrastim 6 mg on day five of chemotherapy are given twice three weeks apart.

Intervention Type PROCEDURE

Consolidation treatment part 1: HD-chemotherapy with ASCT

Consolidation treatment Part 1 starts 4-8 weeks after the second cycle of Induction treatment Part 3.

High dose chemotherapy (HD-chemotherapy) consists of:

BCNU 300 mg/m2 is given on day 1, etoposide 800 mg/m2 divided into four equal doses is given on day 2-5, cytarabine 1600 mg/m2 divided into eight equal doses is given on day 2-5, melphalan 140 mg/m2 is given on day 6.

On day 7, collected stem cells from peripheral blood (see Induction treatment part 1) are infused back to the patient. This is called autologous transplantation (ASCT). Filgrastim 5 ug/kg is given from day 14 (start of the chemotherapy being day 1) until neutrophil recovery.

Intervention Type PROCEDURE

Consolidation treatment part 2: Radiotherapy

Radiotherapy is started given 4-8 weeks after the autologous transplantation. It is given to patients with initially bulky disease (\>10 cm at diagnosis) or to patients with residual disease after Induction treatment part 1-3 and Consolidation treatment part 1. 30-40 Gy are given in 2 Gy fractions over 3-4 weeks.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Aggressive B-cell lymphoma, namely diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma grade III
* Age 18-65 years
* Age-adjusted IPI score 2-3
* ECOG performance status 0-3
* Signed informed consent

Exclusion Criteria

* Burkitt lymphoma
* Posttransplant lymphoproliferation
* Previous treatment (up to one cycle of standard pretreatment with COP, CHOP or steroids permitted and latter mandatory to decrease tumor burden and/or improve performance status)
* Other tumor in previous history with the exception of basalioma, squamous cell carcinoma of the skin or cervical carcinoma in situ
* Pregnancy/lactation
* CNS involvement
* Other serious comorbidities
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, Czech Republic

OTHER_GOV

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Czech Lymphoma Study Group

OTHER

Sponsor Role lead

Principal Investigators

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Pytlik Robert, M.D.

Role: PRINCIPAL_INVESTIGATOR

1st Department of Medicine, General University Hospital, Prague

Marek Trněný, M.D., PhD.

Role: STUDY_DIRECTOR

General University Hospital, Prague

Locations

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University Hospital Brno-Bohunice

Brno, , Czechia

Site Status

Hospital Chomutov

Chomutov, , Czechia

Site Status

Hospital České Budějovice

České Budějovice, , Czechia

Site Status

University Hospital Hradec Králové

Hradec Králové, , Czechia

Site Status

University Hospital Královské Vinohrady

Prague, , Czechia

Site Status

General University Hospital

Prague, , Czechia

Site Status

University Hospital Motol

Prague, , Czechia

Site Status

Hospital Ústí nad Labem

Ústí nad Labem, , Czechia

Site Status

Countries

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Czechia

Related Links

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http://www.lymphoma.cz

Official Site of the Czech Lymphoma Study Group

Other Identifiers

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NR-8231/3

Identifier Type: -

Identifier Source: secondary_id

CLSG 5_02

Identifier Type: -

Identifier Source: org_study_id