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

Inclusion Criteria

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