Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

A Phase II Study of Intensive-Dose Topotecan, Ifosfamide/Mesna and Etoposide (Vepesid)(TIME) Followed by Autologous Stem Cell Rescue in High Risk Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by autologous bone marrow transplantation or peripheral stem cell transplantation in treating patients who have non-Hodgkin's lymphoma or Hodgkin's lymphoma.

OBJECTIVES:

• Determine the efficacy of intensive high dose chemotherapy consisting of topotecan, ifosfamide, and etoposide followed by autologous bone marrow or peripheral blood stem cell transplantation in terms of response rate, progression free survival, and overall survival in patients with high risk non-Hodgkin's lymphoma or Hodgkin's lymphoma.
• Determine the pharmacokinetic profile of high dose topotecan and etoposide in these patients.
• Determine the pharmacodynamics and toxicity of this regimen in these patients.
• Determine the role of either an up or down regulation of DNA topoisomerase I or II amount and/or activity in terms of clinical response and toxicity in patients treated with this regimen.

OUTLINE: Patients receive intensive high dose chemotherapy consisting of ifosfamide IV over 2 hours followed by topotecan IV over 30 minutes on days -8 to -6 and etoposide IV continuously over 24 hours on days -5 to -3. Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0.

Patients are followed at 3, 6, and 12 months, annually until disease relapse, and then every 6 months until death.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-Hodgkin's lymphoma

  • No lymphoblastic lymphoma

  • Under 55 years of age:

    • Intermediate and high grade or aggressive disease that has relapsed and/or failed at least 2 salvage chemotherapy regimens OR
    • Failed to achieve complete response after first line induction chemotherapy and failed at least 1 salvage chemotherapy regimen
    • Low grade or indolent disease that has relapsed or failed to achieve complete response after first line induction chemotherapy and failed more than 2 salvage chemotherapy regimens

  • 55 years of age and over:

    • Intermediate and high grade or aggressive disease that has relapsed and/or failed to achieve complete response after first line induction chemotherapy
    • Low grade or indolent disease that has relapsed or failed to achieve complete response after first line induction chemotherapy OR

• Histologically confirmed Hodgkin's lymphoma

  • Under 55 years of age:

    • Received at least 2 prior salvage chemotherapy regimens

  • 55 years of age and over:

    • Stage III or IV disease that has relapsed or failed to achieve remission after combination induction chemotherapy
    • Prior primary radiotherapy allowed if relapse is high risk (e.g., recurrence in radiation field, B symptoms, or liver or bone marrow involvement)

• No active leptomeningeal involvement or severe symptomatic CNS disease

  • Prior CSF tumor involvement allowed if asymptomatic and no evidence of disease on lumbar puncture or no tumor involvement on MRI of the brain

• Solid tumors and brain metastases allowed

  • No evidence of disease by MRI and physical exam following optimal prior surgery and/or radiotherapy AND
  • At least 3 months since prior radiotherapy NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

• 18 to 64

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2.0 mg/dL*
• SGOT or SGPT no greater than 2.5 times normal*
• No severe hepatic dysfunction NOTE: *Unless due to primary malignancy

Renal:

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No severe cardiac dysfunction
• Ejection fraction at least 50% by MUGA scan
• Essential hypertension controlled by medication allowed

Pulmonary:

• DLCO at least 50% of normal OR
• No symptomatic obstructive or restrictive disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No active infection
• HIV negative
• No insulin dependent diabetes mellitus
• No uncompensated major thyroid or adrenal dysfunction
• No significant skin breakdown from tumor or other disease
• No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Prior doxorubicin or daunorubicin allowed if total dose no greater than 450 mg/m2
• No prior topotecan

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Other:

• No concurrent nitroglycerin preparations for angina pectoris
• No concurrent antiarrhythmic drugs for major ventricular arrhythmias