Three Different Therapy Regimens in Treating Patients With Previously Untreated Hodgkin Lymphoma

Study Characterizing the Impact of Different Therapeutic Strategies on Event Occurrence at 2 Years, 5 Years, 10 Years, and 15 Years, According to Prognostic Groups in Patients With Hodgkin Lymphoma

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 drugs in different combinations may kill more cancer cells. It is not yet know which treatment regimen is more effective in treating Hodgkin lymphoma.

PURPOSE: This phase III trial is studying three different therapy regimens to compare how well they work in treating patients with previously untreated Hodgkin lymphoma.

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Drug: dexamethasone; Drug: carmustine; Drug: etoposide; Drug: cytarabine; Drug: melphalan; Drug: gemcitabine hydrochloride; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: vinorelbine tartrate; Drug: cisplatin; Drug: methylprednisolone; Biological: bleomycin sulfate; Drug: dacarbazine; Drug: ifosfamide; Procedure: autologous hematopoietic stem cell transplantation; Drug: ABVD regimen; Drug: vindesine; Drug: mitoguazone; Procedure: allogeneic hematopoietic stem cell transplantation

Detailed Description

OBJECTIVES:

Primary

• Evaluate event-free survival.

Secondary

• Evaluate overall survival.
• Evaluate the prognostic value of FDG-PET scanning.
• Evaluate progression-free survival.
• Evaluate tolerability.
• Evaluate rate of relapse.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 3 treatment groups according to prognosis.

• Group 1 (favorable prognosis): Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin sulfate IV, vincristine sulfate IV, dacarbazine IV, and methylprednisolone IV on days 1 and 14. Treatment repeats every 28 days for 2 courses. Patients then undergo PET scan for evaluation of response. Patients receive additional treatment according to response.

  • Favorable response: Patients with favorable response receive 1 additional course of ABVD chemotherapy.
  • Unfavorable response: Patients with unfavorable response receive 1 course of VABEM chemotherapy comprising vindesine IV continuously on days 1-5, doxorubicin hydrochloride IV continuously on days 1-3, carmustine IV on day 3, etoposide IV on days 3-5, and methylprednisolone IV on days 1-5.

• Group 2 (intermediate prognosis): Patients receive 2 courses of ABVD chemotherapy. Patients then undergo PET scan for evaluation of response. Patients receive additional treatment according to response.

  • Favorable response: Patients with favorable response receive 4 additional courses of ABVD chemotherapy.
  • Unfavorable response: Patients with unfavorable response receive VABEM chemotherapy. Treatment with VABEM chemotherapy repeats every 28 days for 2 courses.

• Group 3 (poor prognosis): Patients receive 2 courses of VABEM chemotherapy. Patients then undergo PET scan for evaluation of response. Patients receive additional treatment according to response.

  • Favorable response: Patients with favorable response receive 1 additional course of VABEM chemotherapy.

  • Unfavorable response: Patients with unfavorable response receive CEO chemotherapy comprising cisplatin IV continuously on days 1-3, gemcitabine hydrochloride IV on days 1 and 8, and oral dexamethasone once daily on days 1-4. Treatment repeats every 21 days for 3 courses. Patients then undergo PET scan. Patients receive additional treatment according to response.

    • Favorable response: Patients with favorable response receive BEAM chemotherapy comprising carmustine IV on day -7, etoposide IV and cytarabine IV on days -6 to -3, and melphalan IV on day -2. Patients then undergo autologous stem cell transplantation on day 0.
    • Unfavorable response: Patients with unfavorable response receive MINE chemotherapy comprising mitoguazone IV, vinorelbine ditartrate IV, and ifosfamide IV on days 1-5 and etoposide IV on days 1-3. Treatment repeats every 28 days for 3 courses. Patients then undergo allogeneic or autologous stem cell transplantation.

Patients with favorable response or a "bulky" mass at diagnosis may also undergo radiotherapy.

After completion of study treatment, patients are followed periodically for 15 years.

• Study Type: Interventional
• Enrollment (Actual): 442
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Tours Cedex, France, 37044
    • FILO French Innovative Leukemia Organization

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

• Life expectancy > 3 months
• LVEF normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be able to undergo follow-up for ≥ 15 years
• No impaired cardiac function that would preclude the administration of an anthracycline
• No other prior or concurrent malignancy, except for carcinoma in situ of the cervix or basal cell skin cancer
• No respiratory, kidney, or liver failure or other severe clinical insufficiency that would preclude study treatment
• No HIV or hepatitis B virus positivity
• No other disease that would preclude treatment with chemotherapy or radiotherapy

EXCLUSION CRITERIA:

• No concurrent participation in another experimental trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (favorable prognosis); Patients receive ABVD and VABEM chemotherapy.	Drug: carmustine; Given IV; Drug: etoposide; Given IV; Drug: doxorubicin hydrochloride; Given IV; Drug: vincristine sulfate; Given IV; Drug: methylprednisolone; Given IV; Biological: bleomycin sulfate; Given IV; Drug: dacarbazine; Given IV; Drug: ABVD regimen; Given IV; Drug: vindesine; Given IV
Experimental: Group 2 (intermediate prognosis); Patients receive ABVD and VABEM chemotherapy.	Drug: carmustine; Given IV; Drug: etoposide; Given IV; Drug: doxorubicin hydrochloride; Given IV; Drug: vincristine sulfate; Given IV; Drug: methylprednisolone; Given IV; Biological: bleomycin sulfate; Given IV; Drug: dacarbazine; Given IV; Drug: ABVD regimen; Given IV; Drug: vindesine; Given IV
Experimental: Group 3 (poor prognosis); Patients receive VABEM, CEO, BEAM, and MINE chemotherapy. Patients also undergo allogeneic or autologous stem cell transplantation.	Drug: dexamethasone; Given orally; Drug: carmustine; Given IV; Drug: etoposide; Given IV; Drug: cytarabine; Given IV; Drug: melphalan; Given IV; Drug: gemcitabine hydrochloride; Given IV; Drug: doxorubicin hydrochloride; Given IV; Drug: vinorelbine tartrate; Given IV; Drug: cisplatin; Given IV; Drug: methylprednisolone; Given IV; Drug: ifosfamide; Given IV; Procedure: autologous hematopoietic stem cell transplantation; Patients undergo autologous stem cell transplantation; Drug: vindesine; Given IV; Drug: mitoguazone; Given IV; Procedure: allogeneic hematopoietic stem cell transplantation; Patients undergo allogeneic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	event free survival	treatments evaluation

Collaborators and Investigators

• Sponsor: French Innovative Leukemia Organisation
• Investigators: Principal Investigator: Delphine Senecal, French Innovative Leukemia Organization

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 12, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (Estimate): June 15, 2009

Study Record Updates

• Last Update Posted (Estimate): September 16, 2016
• Last Update Submitted That Met QC Criteria: September 15, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Dexamethasone; Methylprednisolone; Etoposide; Ifosfamide; Melphalan; Doxorubicin; Liposomal doxorubicin; Vinorelbine; Cytarabine; Vincristine; Carmustine; Dacarbazine; Bleomycin; Vindesine; Mitoguazone
• Other Study ID Numbers: LH 2007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED