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HIGH DOSE CHEMORADIOTHERAPY WITH PERIPHERAL BLOOD PROGENITOR CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY REFRACTORY, RELAPSED AND POOR PROGNOSIS NON-HODGKIN'S LYMPHOMA


Phase 2
18 Years
65 Years
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

HIGH DOSE CHEMORADIOTHERAPY WITH PERIPHERAL BLOOD PROGENITOR CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY REFRACTORY, RELAPSED AND POOR PROGNOSIS NON-HODGKIN'S LYMPHOMA


OBJECTIVES:

- Determine the efficacy of mobilization using filgrastim (G-CSF) with or without
standard-dose ifosfamide, carboplatin, and etoposide (ICE), conditioning using
ifosfamide and etoposide plus total body irradiation or high-dose ICE, and autologous
peripheral blood stem cell (PBSC) transplantation as salvage therapy in patients with
refractory, recurrent, or poor prognosis non-Hodgkin's lymphoma.

- Determine the efficacy of reinduction comprising ICE followed by autologous PBSC
transplantation in these patients.

- Determine the ability of standard-dose ICE combined with hematopoietic growth factors
to mobilize PBSC in these patients.

- Determine the contamination of PBSC by lymphoma cells in patients treated with this
mobilization regimen.

- Determine the quality of life of patients treated with this regimen.

OUTLINE: Patients are stratified according to disease status (relapsed vs refractory),
lymphoma grade (low vs intermediate vs high), number of extranodal sites, serum lactic
dehydrogenase, performance status, age, and volume of disease.

- Mobilization/harvest: Patients in first or greater complete remission (CR) are treated
on regimen A, whereas patients with recurrent or refractory disease are treated on
regimen B.

- Regimen A: Patients with poor prognosis intermediate-grade lymphoma (IGL) in first
CR or IGL or low-grade lymphoma (LGL) in second or greater CR receive mobilization
with filgrastim (G-CSF) subcutaneously (SC) daily on days 1-7. Autologous
peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells on
days 5 and 6 (and day 7 if needed).

- Regimen B: Patients who are currently on the MSKCC standard dose salvage therapy
protocol with ifosfamide, carboplatin, and etoposide (ICE) for recurrent or
refractory IGL receive additional mobilization with G-CSF after completion of the
last course of ICE. Patients with recurrent or refractory IGL, immunoblastic
lymphoma, or LGL who have not previously received ifosfamide and are not currently
on the MSKCC standard dose salvage protocol with ICE receive ifosfamide IV and
carboplatin on day 2 and etoposide IV on days 1-3 (standard-dose ICE) followed by
G-CSF SC. When blood counts recover, autologous PBSC are harvested and selected
for CD34+ cells.

- Regimens A and B: If additional hematopoietic growth factors (HGFs) become
available, they may be administered concurrently with G-CSF. If inadequate CD34+
cells are collected, then autologous bone marrow is harvested.

- Conditioning: Patients who are under age 60 and have not received dose-limiting
radiotherapy are treated on regimen C. Patients who are age 60 and over and patients
who are under age 60 and have received dose-limiting radiotherapy are treated on
regimen D.

- Regimen C: Patients undergo hyperfractionated total body irradiation twice a day
on days -10 to -7 and ifosfamide IV over 1 hour followed by etoposide IV over 23
hours on days -6 to -2.

- Regimen D: Patients receive ifosfamide IV over 1 hour, followed by etoposide IV
over 11 hours, followed by carboplatin IV over 1 hour, followed by etoposide IV
over 11 hours on days -7 to -3 (high-dose ICE).

- Regimens C and D: Patients with residual or relapsed disease may undergo boost
radiotherapy twice a day, 5 days a week, for 1-2 weeks before conditioning or
after transplantation.

- Transplantation: PBSC or bone marrow is reinfused on day 0. Patients receive G-CSF SC
every 12 hours beginning on day 1 and continuing until blood counts recover. If
additional HGFs become available, they may be administered concurrently with G-CSF.

Quality of life is assessed at baseline and then at 6, 12, and 24 months after
transplantation.

Patients are followed at 1 and 3 months, every 3 months through year 2, every 4 months
through year 5, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 80 patients (20 for regimen A and 60 for regimen B) will be
accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- One of the following diagnoses:

- Histologically proven recurrent non-Hodgkin's lymphoma

- Previously in complete remission (CR)

- Refractory or recurrent intermediate-grade lymphoma (IGL) or high-grade
immunoblastic lymphoma (IBL) meeting 1 of the following conditions:

- In partial remission (PR) or CR to and currently enrolled on the MSKCC
standard dose salvage regimen with ifosfamide, carboplatin, and etoposide
(ICE)

- In PR or CR after 1-2 other salvage chemotherapy regimens (e.g., 3 courses
of dexamethasone, high-dose cytarabine, and cisplatin (DHAP); 2 courses of
cyclophosphamide, mechlorethamine, vincristine, procarbazine, and
prednisone (C-MOPP))

- No prior ifosfamide

- Low-grade lymphoma

- In second or greater remission or chemosensitive relapse

- No HLA identical sibling donor available

- IGL or IBL

- In first CR

- Poor prognosis, defined by age-adjusted international index of 3 or 4 based
on lactic dehydrogenase, number of extranodal sites, stage, and performance
status

- Adequate bone marrow cellularity

- No lymphoblastic or small noncleaved cell lymphoma

- Ineligible for total body irradiation (TBI) phase of study if prior radiotherapy dose
precludes the use of TBI 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:

- Physiologic 18 to 65

Performance status:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin no greater than 2.0 mg/dL (if no history of Gilbert's disease)

- No chronic active or persistent hepatitis

- Hepatitis B positivity allowed provided that the following conditions are met:

- Bilirubin same as above*

- SGPT no greater than 500 IU/L*

- Alkaline phosphatase no greater than 2 times normal* NOTE: * In the absence of
liver involvement by lymphoma

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 60 mL/min

- No history of chronic renal insufficiency

Cardiovascular:

- LVEF at least 50% by echocardiogram or MUGA scan

- No myocardial infarction within the past 6 months

- No unstable angina

- No arrhythmia other than chronic atrial fibrillation

Pulmonary:

- DLCO at least 50% predicted (corrected for hemoglobin and alveolar ventilation)

Other:

- HIV negative

- No uncontrolled infection

- No other malignancy within the past 5 years except curatively treated basal cell skin
cancer or carcinoma in situ of the cervix

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

Surgery

- Not specified

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Craig Moskowitz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000064483

NCT ID:

NCT00002697

Start Date:

September 1995

Completion Date:

Related Keywords:

  • Lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021