Combination Chemotherapy in Treating Patients With Advanced Hodgkin's Lymphoma

A Phase II Pilot Study of Short Term (12 Week) Combination Chemotherapy (Stanford V) in Unfavorable Hodgkin's Disease

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have advanced Hodgkin's lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Stanford V regimen; Biological: Bleomycin sulfate; Drug: Doxorubicin hydrochloride; Drug: Etoposide; Drug: Mechlorethamine hydrochloride; Drug: Prednisone; Drug: Vinblastine; Drug: Vincristine sulfate

Detailed Description

OBJECTIVES:

• Determine the feasibility of short term chemotherapy with the Stanford V regimen (mechlorethamine, doxorubicin, vinblastine, prednisone, vincristine, bleomycin, and etoposide) followed by, as indicated, consolidative radiotherapy in patients with stage IIB, IIIA, IIIB, or IV Hodgkin's lymphoma.
• Determine the initial response to 8 weeks of Stanford V chemotherapy in these patients.
• Assess the complete and partial response rate to 12 weeks of Stanford V chemotherapy in these patients.
• Determine the acute toxicity associated with this treatment.
• Determine the disease free interval and survival following Stanford V chemotherapy with or without consolidative radiotherapy in these patients.

OUTLINE: All patients are treated on Regimen A with the Stanford V Regimen; those with initial bulky, residual, or splenic disease who achieve a CR/PR proceed to Regimen B.

• Regimen A: Patients receive mechlorethamine IV on weeks 1, 5, and 9; doxorubicin and vinblastine IV on weeks 1, 3, 5, 7, 9, and 11; vincristine and bleomycin IV on weeks 2, 4, 6, 8, 10, and 12; etoposide IV over 30-45 minutes for 2 consecutive days on weeks 3, 7, and 11; and prednisone orally every other day on days 1-84. Treatment continues for 8-12 weeks, depending on response, in the absence of disease progression or unacceptable toxicity.
• Regimen B: Patients begin radiotherapy 2-4 weeks after completion of Regimen A. Patients receive radiotherapy to lungs, pleura, and other extralymphatic sites for approximately 5 weeks.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 50 patients will be entered if at least 16 of the first 22 patients respond. As of 03/96, it is expected that a total of 45 patients each with stage III/IV disease and 40 with unfavorable stage II disease will be accrued.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center at Stanford University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma of any histology

• Unfavorable disease required

  • Clinical stage IIIA, IIIB, IV, or IIB (non-bulky)

  • Locally extensive stage I or II with either of the following:

    • Mediastinal mass greater than 1/3 the maximum intrathoracic diameter
    • Two or more extranodal sites

PATIENT CHARACTERISTICS:

Age:

• 18 to 60

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No prior malignancy except nonmelanomatous skin cancer
• No significant concurrent illness that precludes protocol participation

PRIOR CONCURRENT THERAPY:

• No prior treatment for Hodgkin's lymphoma

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination Chemotherapy (Stanford V); A combination chemotherapy regimen consisting of mechlorethamine, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide and prednisone, administered on a compressed schedule

Drug: Stanford V regimen; Biological: Bleomycin sulfate; A component of the Stanford V regimen.; Drug: Doxorubicin hydrochloride; A component of the Stanford V regimen.; Drug: Etoposide; A component of the Stanford V regimen.; Drug: Mechlorethamine hydrochloride; A component of the Stanford V regimen.; Drug: Prednisone; A component of the Stanford V regimen.; Drug: Vinblastine; A component of the Stanford V regimen.; Drug: Vincristine sulfate; A component of the Stanford V regimen.

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Horning SJ, Rosenberg SA, Hoppe RT. Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: an update. Ann Oncol. 1996;7 Suppl 4:105-8. doi: 10.1093/annonc/7.suppl_4.s105.
• Bartlett NL, Rosenberg SA, Hoppe RT, Hancock SL, Horning SJ. Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report. J Clin Oncol. 1995 May;13(5):1080-8. doi: 10.1200/JCO.1995.13.5.1080.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 1989
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Stage I adult Hodgkin lymphoma; Stage II adult Hodgkin lymphoma; Stage III adult Hodgkin lymphoma; Stage IV adult Hodgkin lymphoma; Adult lymphocyte predominant Hodgkin lymphoma; Adult lymphocyte depletion Hodgkin lymphoma; Adult nodular sclerosis Hodgkin lymphoma; Adult mixed cellularity Hodgkin lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Etoposide; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine; Bleomycin; Vinblastine; Mechlorethamine
• Other Study ID Numbers: IRB-13467; SUMC-G2/G3 (Other Identifier: Stanford University Medical Center); CDR0000064551 (Other Identifier: Stanford University Medical Center); SQL 76234 (Other Identifier: Stanford University Medical Center); NCI-H96-0806 (Other Identifier: Old NCI)