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Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy With Interleukin-2 Versus Observation for Patients With Non-Hodgkin's Lymphoma


Phase 3
16 Years
60 Years
Not Enrolling
Both
Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma

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Trial Information

Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy With Interleukin-2 Versus Observation for Patients With Non-Hodgkin's Lymphoma


PRIMARY OBJECTIVES:

I. To compare the survival and disease-free survival of patients with non-Hodgkin's lymphoma
treated with post-transplant therapy with interleukin-2 (IL-2) or no further treatment.
Transplant therapy is total body irradiation (TBI), high-dose etoposide, cyclophosphamide
and peripheral blood stem cell transplant (PBSCT).

II. To assess the frequency and severity of toxicity associated with post-transplant IL-2
therapy.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
disease grade (low vs intermediate vs high), chemosensitive disease (yes vs no), partial or
complete response after initial induction chemotherapy (yes vs no), and performance status
(0-1 vs 2).

Part I: Autologous peripheral blood stem cells (PBSC) are harvested before study entry.
Patients undergo total body irradiation twice a day on days -8 to -5, high-dose etoposide IV
over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2. PBSC are reinfused on
day 0 and then filgrastim (G-CSF) may be administered subcutaneously or IV on days 0-21.

Part II: Within 28-80 days after PBSC transplantation and after recovery from any toxic
effects, patients with no active recurrent or progressive disease are randomized to 1 of 2
treatment arms.

Arm I: Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.

Arm II: Patients undergo observation only.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then
annually thereafter.

PROJECTED ACCRUAL: Approximately 275 patients will be accrued for this study within 3.5-5.9
years.


Inclusion Criteria:



- REGISTRATION # 1

- All patients must have biopsy proven diagnosis of low, intermediate or high grade
malignant non-Hodgkin's lymphoma; transformed lymphomas are eligible

- Patients with histologic diagnosis of working formulation A (malignant lymphoma small
lymphocytic) or working formulation I (malignant lymphoma, lymphoblastic) are not
eligible

- Patients must have relapsed after achieving a complete or partial response to prior
therapy, or have never responded to prior therapy

- Patients must have debulking (salvage) chemotherapy to determine if the disease is
sensitive to chemotherapy; the sole exception to this requirement is for patients
with intermediate or high grade lymphoma (working formulation D - H or J) whose
disease did not respond to, or progressed during, INITIAL chemotherapy

- Prior therapy is required; concurrent therapy is NOT permitted

- Patients with low grade lymphoma (working formulation B or C) must have received
at least two prior chemotherapy regimens; if the patient has had one or more CR,
then the most recent CR must have been less than one year in duration

- Patients with intermediate or high grade non-Hodgkin's lymphoma (working
formulation D - H or J) must have received at least one prior chemotherapy
regimen

- NOTE: Debulking chemotherapy given only to determine sensitivity is not
considered in the calculation of number of prior regimens

- Patients must have a bone marrow aspirate and biopsy obtained within 42 days of stem
cell collection or within 42 days prior to registration

- Patients with a history of seizures or central nervous system involvement by lymphoma
are NOT eligible

- Only patients with a normal cardiac history and physical exam or in lieu of this, an
institutionally normal ejection fraction as measured by either ECHO or MUGA scan are
eligible; specifically, there should be: no EKG evidence of active cardiac disease
(i.e., arrhythmias, ischemia), no history of congestive heart failure (CHF), no
history of myocardial infarction or ischemia, no history of arrhythmia (other than
bradycardia treated by pacing), no current cardiac medications for the control of CHF
or arrhythmias, no S3 gallop rhythm, or peripheral edema, and no chest X-ray findings
compatible with CHF; EKG must be performed within 42 days prior to registration

- All patients must have a pretreatment serum creatinine of =< 1.5 times the
institutional upper limit of normal measured after completion of prior therapy and
within 28 days prior to registration

- Patients must have adequate pulmonary function as measured by a DLCO >= 65% of
predicted or FEV1 >= 65% of predicted measured after completion of prior therapy and
within 120 days prior to registration

- Patients must have adequate hepatic function as measured by a bilirubin of =< 1.5 x
the institutional upper limit of normal and SGOT or SGPT =< 2 x the institutional
upper limit of normal, measured after completion of prior therapy and within 28 days
prior to registration

- Patients who have undergone previous bone marrow transplantation or autologous
peripheral blood stem cell transplantation are NOT eligible

- Patients who have undergone previous therapy with interleukin-2 are NOT eligible

- Patients must have recovered from the nadir resulting from the last cancer therapy;
this will generally be at least four weeks from prior radiation or chemotherapy, and
six weeks from nitrosoureas

- Patients must have a Southwest Oncology Group performance status of 0 or 1

- Patients must have a CT scan of the chest, abdomen and pelvis performed within 28
days prior to registration and at least 21 days after the completion of prior
chemotherapy (excluding mobilization therapy)

- Patients must have LDH performed within 28 days prior to registration and at least 21
days after completion of prior chemotherapy (excluding mobilization therapy)

- Patients must have undergone an adequate collection of peripheral blood stem cells
(PBSC) according to accepted procedures at each individual institution

- Patients with known allergy to etoposide or a history of grade 3 hemorrhagic cystitis
with cyclophosphamide are not eligible

- Patients who have received prior involved field irradiation prohibiting the use of
TBI are not eligible

- Patients must be negative for antibody to HIV and this test must have been performed
within 42 days prior to registration; patients must not have an autoimmune disease or
have had a prior allogeneic (from someone else) organ or tissue transplant

- If day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next
working day; in calculating days of tests and measurements, the day a test or
measurement is done is considered day 0; therefore, if a test is done on a Monday,
the Monday four weeks later would be considered day 28; this allows for efficient
patient scheduling without exceeding the guidelines

- No prior malignancy is allowed except for adequately treated basal cell (or squamous
cell) skin cancer, in situ cervical cancer or other cancer for which the patient has
been disease-free for five years

- Pregnant or nursing women may not participate; women or men of reproductive potential
may not participate unless they have agreed to use an effective contraceptive method

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines

- At the time of patient registration, the treating institution's name and ID number
must be provided to the statistical center in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered into the database

- REGISTRATION # 2 (RANDOMIZATION)

- Patients who are less than 28 days or more than 80 days after PBSCT will not be
registered for randomization

- Patients known to be ineligible for registration step #1 may not be registered to
registration step #2

- Restaging radiographic studies are not required between PBSCT and registration #2
(randomization), however, patients with known active recurrent or progressive disease
are not eligible for randomization

- ANC > 500 mm^3

- Platelet count supportable to > 20,000/mm^3 with no more than one transfusion per day

- The patient must be free of active bacterial, fungal or viral infection, afebrile,
off antibiotics, antifungal and antiviral agents (with the exception of prophylactic
therapy) for three consecutive days

- Bilirubin =< 2 times the institutional upper limit of normal; test must be completed
within 7 days prior to registration

- SGOT or SGPT =< 2 times the institutional upper limit of normal; test must be
completed within 7 days prior to registration

- Alkaline phosphatase =< 2 times the institutional upper limit of normal; test must be
completed within 7 days prior to registration

- Creatinine =< 1.5 times the institutional upper limit of normal; test must be
completed within 7 days prior to registration

- The patient must have =< grade 1 cardiac, pulmonary, CNS, renal, hepatic, GI toxicity
and < grade 3 mucosal toxicity according to the Southwest Oncology Group Toxicity
Criteria

- The patient must have received no amphotericin B, corticosteroids, pentoxifylline, or
growth factors for at least 72 hours prior to registration

- The patient must have a current Southwest Oncology Group performance status of 0-2

- Patients must have an EKG with no active cardiac disease and a chest x-ray with no
active pulmonary disease; these tests must be completed within 7 days prior to
registration

- Patients must not have an autoimmune disease or have had a prior allogeneic (from
someone else) organ or tissue transplant

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

Up to 13 years

Safety Issue:

No

Principal Investigator

John Thompson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03072

NCT ID:

NCT00002649

Start Date:

May 1995

Completion Date:

Related Keywords:

  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Burkitt Lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Southwest Oncology GroupSan Antonio, Texas  78245