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Phase II Study of Intensive Carmustine and Etoposide With Cisplatin or Cyclophosphamide, Followed By Rescue With Autologous Bone Marrow Treated In Vitro With Etoposide and/or Peripheral Blood Stem Cells Mobilized With Filgrastim (G-CSF) or Sargramostim (GM-CSF) With or Without Radiotherapy in Patients With Resistant Hodgkin's Disease or Non-Hodgkin's Lymphoma


Phase 2
15 Years
65 Years
Open (Enrolling)
Both
Lymphoma

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Trial Information

Phase II Study of Intensive Carmustine and Etoposide With Cisplatin or Cyclophosphamide, Followed By Rescue With Autologous Bone Marrow Treated In Vitro With Etoposide and/or Peripheral Blood Stem Cells Mobilized With Filgrastim (G-CSF) or Sargramostim (GM-CSF) With or Without Radiotherapy in Patients With Resistant Hodgkin's Disease or Non-Hodgkin's Lymphoma


OBJECTIVES: I. Determine the antitumor activity of intensive carmustine and etoposide with
cisplatin or cyclophosphamide, followed by rescue with autologous bone marrow (ABM) treated
in vitro with etoposide and/or peripheral blood stem cells mobilized with filgrastim (G-CSF)
or sargramostim (GM-CSF) with or without radiotherapy in patients with refractory Hodgkin's
disease or non-Hodgkin's lymphoma. II. Determine the time to recovery of peripheral blood
counts in patients treated with this regimen. III. Correlate the rate of peripheral blood
cell recovery in these patients with in vitro growth of ABM treated with etoposide.

OUTLINE: This is a multicenter study. Autologous bone marrow (ABM) is harvested and
two-thirds of the ABM is treated in vitro with etoposide (VP-16). ABM may have been stored
earlier in the course of the disease for patients who are at high risk of relapse or who
were previously treated with agents causing bone marrow or stem cell damage (e.g.,
nitrosoureas, pelvic irradiation). Patients with prior bone marrow involvement and
subsequent bone marrow remission must have received 1 or 2 additional courses of the same
chemotherapy before undergoing harvest of ABM. Patients for whom PBSC rescue alone is
planned also undergo ABM harvest in case back-up ABM rescue is needed. Patients then receive
sargramostim (GM-CSF) or filgrastim (G-CSF) subcutaneously beginning 5 days before harvest
of peripheral blood stem cells (PBSC) and continuing until completion of harvest. Patients
without extensive prior radiotherapy undergo radiotherapy to areas of measurable active
disease plus a 2 cm margin on days -21 to -17 and -14 to -8. Patients without a
contraindication to cisplatin (e.g., hearing impairment, peripheral neuropathy) receive
cisplatin IV over 3 hours on days -7 to -3 and carmustine IV over 2 hours and VP-16 IV over
4 hours on days -6 to -4. Patients with a contraindication to cisplatin receive
cyclophosphamide IV every 12 hours, VP-16 IV over 1 hour every 12 hours, and carmustine IV
over 1 hour on days -7 to -4. ABM and/or PBSC are reinfused on day 0. The first 6 ABM rescue
patients receive untreated ABM and subsequent patients receive ABM treated in vitro with
VP-16. Patients with bone marrow biopsy showing no evidence of regeneration (marrow
cellularity less than 1%) at day 21 after PBSC rescue undergo back-up ABM rescue. Patients
without engraftment (granulocyte count less than 500/mm3 and untransfused platelets no
greater than 20,000/mm3) by day 28 after rescue with ABM treated in vitro with VP-16 undergo
rescue with untreated ABM.

PROJECTED ACCRUAL: A total of 21-46 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Diagnosis of resistant Hodgkin's disease Eligible subtypes:
Lymphocytic predominance Nodular sclerosing Mixed cellularity Lymphocyte depleted Not
otherwise specified Must meet 1 of the following conditions: Disease progression after at
least 1 course of prior therapy on each of 2 regimens comprising combination chemotherapy
or radiotherapy Less than a partial remission (PR) after at least 2 courses on each of 2
regimens Failure to achieve a complete remission (CR) after 6 courses of 1 or 2 regimens
Relapse less than 1 year off initial therapy OR Diagnosis of intermediate- or high-grade
non-Hodgkin's lymphoma (NHL) Eligible subtypes: Diffuse poorly differentiated lymphocytic
Diffuse mixed lymphocytic-histiocytic Nodular histiocytic Diffuse histiocytic Diffuse
undifferentiated Lymphoblastic Must meet 1 of the following conditions: Disease
progression after 1 course of prior therapy Failure to achieve a PR after 2 courses of
prior therapy Failure to achieve a CR after 6 courses of prior therapy OR Diagnosis of
low-grade NHL Eligible subtypes: Diffuse well-differentiated lymphocytic Nodular poorly
differentiated lymphocytic Nodular mixed lymphocytic-histiocytic Failure on second-line
therapy administered for progressive symptomatic disease or organ compromise Measurable
disease by physical exam, external imaging or scanning studies, or tumor markers No severe
symptomatic CNS disease of any etiology History of prior CNS tumor allowed if no signs or
symptoms at study entry Active CNS lymphoma (meningeal lymphomatosis) rendered
disease-free by conventional therapies allowed Epidural metastases or discrete parenchymal
brain lesions allowed if tumors can be encompassed in standard treatment fields Bilateral
marrow core biopsy free of tumor and showing at least 30% cellularity Prior marrow
involvement allowed if marrow is histologically normal at time of storage No significant
skin breakdown due to tumor or other disease 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: 15 to 65 Performance status: Karnofsky 70-100% OR ECOG 0-1
Life expectancy: At least 8 weeks without transplantation Hematopoietic: Granulocyte count
at least 1,500/mm3 Platelet count at least 150,000/mm3 Hepatic: Bilirubin no greater than
1.8 mg/dL SGOT and SGPT less than 2 times normal No high risk for veno-occlusive disease
of the liver Renal: No severe renal dysfunction unless due to tumor invasion Creatinine no
more than 1.5 mg/dL Creatinine at least 60 mL/min Cardiovascular: No severe cardiovascular
dysfunction unless due to tumor invasion No myocardial infarction within the past 6 months
No symptoms of major heart disease Ejection fraction at least 50% by MUGA scan Essential
hypertension controlled with medication allowed Pulmonary: No severe pulmonary dysfunction
unless due to tumor invasion DLCO at least 50% normal No symptomatic obstructive or
restrictive pulmonary disease Other: No insulin-dependent diabetes mellitus No
uncompensated major thyroid or adrenal dysfunction No active infection HTLV-III negative
(no AIDS-related complex)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics At least 4 weeks since prior chemotherapy (at least 6 weeks since prior
nitrosoureas or mitomycin) Prior exposure to etoposide, cisplatin, or carmustine allowed
if cumulative dose of chloroethylnitrosourea (carmustine or lomustine) no greater than 400
mg/m2 Prior doxorubicin or daunorubicin dose of 450 mg/m2 or more allowed if LVEF at least
50% No concurrent chemotherapy Endocrine therapy: Concurrent corticosteroids for
hypercalcemia allowed Radiotherapy: See Disease Characteristics No prior whole-pelvic
radiotherapy Other prior radiotherapy allowed Surgery: Not specified Other: No concurrent
nitroglycerin preparations for angina pectoris No concurrent antiarrhythmic drugs for
major ventricular arrhythmias

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Rasim Ahmet Gucalp, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Albert Einstein College of Medicine of Yeshiva University

Authority:

United States: Federal Government

Study ID:

CDR0000075725

NCT ID:

NCT00002461

Start Date:

April 1988

Completion Date:

Related Keywords:

  • Lymphoma
  • recurrent adult Hodgkin lymphoma
  • adult lymphocyte predominant Hodgkin lymphoma
  • adult lymphocyte depletion Hodgkin lymphoma
  • adult nodular sclerosis Hodgkin lymphoma
  • adult mixed cellularity Hodgkin 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 adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent mantle cell lymphoma
  • recurrent small lymphocytic lymphoma
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Non-Hodgkin

Name

Location

Albert Einstein Comprehensive Cancer CenterBronx, New York  10461