Combination Chemotherapy in Treating Young Patients With Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Radiation: fludeoxyglucose F 18Radiation: radiation therapy
- Registration Number
- NCT00433459
- Lead Sponsor
- Christine Mauz-Körholz
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to compare how well they work in treating young patients with Hodgkin's lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* Determine whether the 5-year event-free survival (EFS) rate in pediatric patients with Hodgkin's lymphoma with an adequate response after 2 courses of vincristine, etoposide, prednisone, and doxorubicin hydrochloride (OEPA) (without radiotherapy) are consistent with an estimated target EFS rate of 90%.
* Compare the EFS (without a deterioration) of patients treated with procarbazine hydrochloride vs dacarbazine (treatment groups 2 and 3).
* Determine the treatment outcome of a standardized risk-adapted relapse strategy in these patients.
Secondary
* Determine whether the 5-year EFS rate in patients with Hodgkin's lymphoma with an inadequate response after 2 OEPA courses and standard involved-field radiotherapy are consistent with an estimated target EFS rate of 90%.
* Determine whether a positive positron emission tomography scan before planned high-dose chemotherapy with autologous stem cell transplantation has a negative prognostic significance.
* Compare the effect of dacarbazine vs procarbazine on the rate of infertility in males and premature menopause in females (treatment groups 2 and 3).
Tertiary
* Determine the impact of real-time central staging and response assessment on treatment outcome in these patients.
OUTLINE: This is a randomized, controlled, parallel-group, open-label, multicenter study. Patients are stratified according to staging and response assessment (central vs local) and disease stage (IA/B or IIA \[first-line treatment group 1\] vs I_EA/B, II_EA, IIB, or IIIA \[first-line treatment group 2\] vs II_EB, III_E A/B, IIIB, or IVA/B \[first-line treatment group 3\]).
* First-line treatment group 1: Patients receive oral prednisone (or prednisolone) 3 times daily on days 1-15, vincristine IV on days 1, 8, and 15, doxorubicin hydrochloride IV over 1-6 hours on days 1 and 15, and etoposide (or etoposide phosphate) IV over 1-2 hours on days 1-5 (OEPA).
Treatment repeats every 28 days for 2 courses in the absence of unacceptable toxicity. Patients are assessed by fludeoxyglucose F 18 positron emission tomography (\^18FDG-PET) scan. Patients with inadequate response undergo radiotherapy within 35 days after completion of OEPA.
* First-line treatment group 2: Patients receive OEPA as in group 1. After completion of OEPA, patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral prednisone (or prednisolone) 3 times daily and oral procarbazine hydrochloride 2-3 times a day on days 1-15 and vincristine IV and cyclophosphamide IV over 1 hour on days 1 and 8 (COPP).
* Arm II: Patients receive oral prednisone (or prednisolone) 3 times daily on days 1-15, dacarbazine IV over 15-30 minutes on days 1-3, and vincristine IV and cyclophosphamide IV over 1 hour on days 1 and 8 (COPDAC).
In both arms, treatment repeats every 28 days for 2 courses in the absence of unacceptable toxicity. Patients are assessed by \^18FDG-PET scan. Patients with an inadequate response undergo radiotherapy within 35 days after completion of COPP or COPDAC.
* First-line treatment group 3: Patients receive OEPA as in group 1. After completion of OEPA, patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive COPP as in arm I of group 2.
* Arm II: Patients receive COPDAC as in arm II of group 2. In both arms, treatment repeats every 28 days for 4 courses in the absence of unacceptable toxicity. Patients are assessed by \^18FDG-PET scan. Patients with an inadequate response undergo radiotherapy within 35 days after completion of COPP or COPDAC.
Patients with biopsy-confirmed disease progression OR relapse after first-line treatment on this study or on protocols DAL-HD 90, GPOH-HD 95, GPOHHD 2002 Pilot, or similar treatment proceed to second-line therapy. Patients are stratified according to relapse/progression status (late relapse from first-line treatment group 1 \[second-line treatment group 1\] vs early relapse from first-line treatment groups 1, 2, or 3 or late relapse from first-line treatment groups 2 or 3 \[second-line treatment group 2\] vs disease progression \[second-line treatment group 3\]). Patients undergo a \^18FDG-PET scan prior to beginning second-line therapy.
* Second-line treatment group 1: Patients receive ifosfamide IV over 22 hours and etoposide IV over 1-2 hours and oral prednisone three times daily on days 1-5 (IEP). Patients then receive doxorubicin hydrochloride IV over 1-6 hours, bleomycin IV, vinblastine IV, and dacarbazine IV over 15-30 minutes on days 22 and 36 (ABVD). Treatment repeats every 50 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After chemotherapy treatment, patients undergo radiotherapy.
* Second-line treatment group 2: Patients receive IEP and ABVD as in group 1. Autologous stem cells are collected after course 1 or 2 of IEP/ABVD.
After chemotherapy, patients with an adequate response undergo radiotherapy. Patients with an inadequate response undergo high-dose chemotherapy comprising carmustine IV over 1-2 hours on day -7, etoposide IV and cytarabine IV over 30 minutes twice daily on days -6 to -3, and melphalan IV over 1½ hours on day -2. Patients then undergo autologous hematopoietic stem cell transplantation (HSCT).
Patients undergo a \^18FDG-PET scan on day 50-54. Patients with \^18FDG-PET scan positive disease undergo radiotherapy.
* Second-line treatment group 3: Patients receive IEP and ABVD as in group 1. All patients then undergo high-dose chemotherapy and HSCT as in group 2.
Patients undergo a \^18FDG-PET scan on day 50-54. Patients with \^18FDG-PET scan positive disease undergo radiotherapy.
After completion of study therapy, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 2,150 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2134
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description COPP procarbazine hydrochloride procarbazine-containing consolidation chemotherapy arm COPP vincristine sulfate procarbazine-containing consolidation chemotherapy arm COPP fludeoxyglucose F 18 procarbazine-containing consolidation chemotherapy arm COPP radiation therapy procarbazine-containing consolidation chemotherapy arm COPDAC vincristine sulfate procarbazine-free consolidation chemotherapy arm COPDAC fludeoxyglucose F 18 procarbazine-free consolidation chemotherapy arm COPDAC radiation therapy procarbazine-free consolidation chemotherapy arm COPP cyclophosphamide procarbazine-containing consolidation chemotherapy arm COPP prednisone procarbazine-containing consolidation chemotherapy arm COPP prednisolone procarbazine-containing consolidation chemotherapy arm COPDAC dacarbazine procarbazine-free consolidation chemotherapy arm COPDAC cyclophosphamide procarbazine-free consolidation chemotherapy arm COPDAC prednisone procarbazine-free consolidation chemotherapy arm COPDAC prednisolone procarbazine-free consolidation chemotherapy arm
- Primary Outcome Measures
Name Time Method Event-free survival 5 years
- Secondary Outcome Measures
Name Time Method Progression-free survival 5 years CTC (Common toxicity criteria) toxicity levels of therapy elements 5 years Evidence of male infertility score 5 years Evidence of female infertility score 5 years Overall survival 5 years Long-term consequences (e.g., premature menopause, secondary cancer) 5 years
Trial Locations
- Locations (2)
Royal Hospital for Sick Children
🇬🇧Edinburgh, Scotland, United Kingdom
Universitaetsklinikum Giessen-Marburg
🇩🇪Giessen, Germany