Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	FCCC-98052 NCI-G99-1541, NCT00003957

Objectives

I.  Determine how many patients with chemotherapy sensitive relapsed 
non-Hodgkin's lymphoma receiving sequential high dose chemotherapy achieve a 
collection of a minimum 5 million CD34+ cells/kg in one large volume 
apheresis. 

II.  Determine the feasibility and safety of this regimen in these patients.

III.  Determine disease free and overall survival of patients receiving this 
regimen.

Entry Criteria

Disease Characteristics:

Histologically confirmed follicular or diffuse large cell, diffuse mixed, or
immunoblastic non-Hodgkin's lymphoma (working formulation D, F, G, or H)
 
First relapse from a complete response or complete response unconfirmed after
a front line chemotherapy regimen (e.g., CHOP-like regimen) 

Second relapse from partial response after 2-4 courses of second line standard
dose chemotherapy (e.g., MINE, EPOCH, or platinum-containing regimens)

No more than 1 salvage treatment regimen

No CNS involvement

Prior/Concurrent Therapy:

Biologic therapy:
 At least 1 week since prior hematopoietic growth factors

Chemotherapy:
 See Disease Characteristics
 At least 4 weeks since prior chemotherapy

Endocrine therapy:
 Not specified

Radiotherapy:
 No prior radiotherapy to relapsed sites of vital organs (except as part of
  initial treatment)
 At least 4 weeks since prior palliative radiotherapy to bulky nodes

Surgery:
 At least 2 weeks since prior major surgery

Other:
 No other concurrent investigational drugs
 No concurrent beta adrenergic blocking agents

Patient Characteristics:

Age:
 18 and over

Performance status:
 ECOG 0-1

Life expectancy:
 Not specified

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Transaminases no greater than 2 times upper limit of normal
 Bilirubin no greater than 2 mg/dL (unless due to biopsy proven lymphoma)
 No chronic viral hepatitis

Renal:
 Creatinine no greater than 1.5 mg/dL OR
 Creatinine clearance at least 60 mL/min
 No overt renal insufficiency

Cardiovascular:
 LVEF at least 45%
 No congestive heart failure (New York Heart Association class III or IV)
 No myocardial infarction within past 6 months
 No uncontrolled hypertension (diastolic blood pressure greater than 115 mmHg)
 No unstable angina
 No coronary angioplasty within past 6 months
 No uncontrolled atrial or ventricular cardiac arrhythmias

Pulmonary:
 DLCO and FEV1 at least 45% of predicted
 No severe pulmonary disease
 No seasonal or recurrent asthma within past 10 years
  No asthmatic symptoms (e.g., wheezing) related to current respiratory
   tract infection
 No concurrent symptoms of bronchoconstriction
 No anaphylactic/anaphylactoid-type event manifested by disseminated
  urticaria, laryngeal edema, and/or bronchospasm 

Other:
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception
 HIV negative
 No prior malignancy within the past 5 years except carcinoma in situ of the
  cervix or basal cell or squamous cell skin cancer
 No severe medical or psychiatric illness (including severe depression)
 No active peptic ulcer disease
 No poorly controlled diabetes
 No allergy to insect vemons 
 No active history of angioedema or recurrent urticaria (an isolated episode
  of urticaria is allowed)
 No active infection
 No fever greater than 38.2 degrees C (except fevers due to B symptoms)
 No allergy to E. coli derived products

Expected Enrollment

A total of 12 patients will be accrued for this study.

Outline

Patients receive cyclophosphamide IV over 1 hour followed by paclitaxel IV 
over 24 hours on day 1.  Filgrastim (G-CSF) and stem cell factor (SCF) are 
administered subcutaneously beginning on day 3 for approximately 7-14 days 
(until the completion of leukapheresis).  Peripheral blood stem cells (PBSC) 
are collected over 3-5 days.

Three weeks after leukapheresis is completed, patients receive cytarabine IV 
over 2 hours twice a day on days -6 to -3.  Mitoxantrone IV is administered 
over 1 hour on day -6. CD34+ PBSC are reinfused on day 0.  

Four weeks later, patients receive etoposide IV over 11 hours on day -2 and 
melphalan IV over 30 minutes twice on day -1.  CD34+ PBSC are reinfused on day 
0. 

Concurrent G-CSF is administered subcutaneously and continues until blood 
counts recover.

Patients are followed at 4 weeks, every 3 months for the first 2 years, and 
then every 6 months for the next 2 years.  

Trial Contact Information

Trial Lead Organizations

Fox Chase Cancer Center - Philadelphia

Russell Schilder, MD, Protocol chair		Ph: 215-728-3545; 888-369-2427 Email: russell.schilder@fccc.edu

Registry Information
Official Title		A Phase II Trial of Multiple Cycles of Sequential High Dose Chemotherapy for Patients with Chemotherapy Sensitive Relapsed Non-Hodgkin's Lymphoma
Trial Start Date		1998-12-24
Registered in ClinicalTrials.gov		NCT00003957
Date Submitted to PDQ		1999-06-24
Information Last Verified		2000-11-01