Combination Chemotherapy With or Without Total-Body Irradiation Followed By Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

Phase 2

Completed

Conditions: Lymphoma

Interventions: Drug: cyclophosphamide
Drug: carmustine
Drug: etoposide
Procedure: autologous hematopoietic stem cell transplantation
Radiation: total-body irradiation
Procedure: peripheral blood stem cell transplantation
Drug: G-CSF

Registration Number: NCT00559104

Lead Sponsor: City of Hope Medical Center

Brief Summary: RATIONALE: Giving chemotherapy and radiation therapy to the entire body before an autologous peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. The patient's stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with or without total-body irradiation followed by a stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma.

Detailed Description: OBJECTIVES:

* To evaluate the outcome of patients with poor-risk, age-adjusted International Prognostic Index high- and high-intermediate-risk, intermediate- and high-grade non-Hodgkin lymphoma undergoing high-dose therapy comprising etoposide and cyclophosphamide, either carmustine or total-body irradiation, and autologous stem cell transplantation (ASCT) given as a consolidation therapy.

* To evaluate the role of high-dose therapy and ASCT during first partial or complete remission (1PR/CR) in patients with poor-risk primary mediastinal large cell lymphoma.

* To evaluate the role of high-dose therapy and ASCT during first 1PR/CR in patients with advanced-stage mantle cell lymphoma.

* To evaluate the short-term and long-term toxicities of high-dose therapy and ASCT when performed during 1PR/CR in patients with poor-risk aggressive lymphomas.

OUTLINE: Patients are stratified according to disease (diffuse mixed, diffuse large cell, and immunoblastic lymphoma vs primary mediastinal large cell lymphoma vs small noncleaved cell lymphoma vs stage IV mantle cell lymphoma).

Patients' peripheral blood stem cells (PBSC) are collected after mobilization. A minimum of 2.0 x 10\^6 CD34+ cells/kg must be collected. Patients experiencing disease progression during stem cell collection will be removed from study. Patients are assigned to undergo 1 of 2 therapeutic regimens.

* Regimen 1: Patients undergo total-body irradiation (TBI) on days -8 to -5 and receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous PBSC transplantation on day 0.

* Regimen 2 (for patients who have received any prior thoracic irradiation or patients who underwent previous irradiation that precludes the use of TBI): Patients receive carmustine IV over 2 hours on days -7 to -5. Patients then receive etoposide and cyclophosphamide and undergo autologous PBSC transplantation as in regimen 1.

Patients with residual bulky disease greater than 5 cm may undergo involved-field radiotherapy before or after transplantation.

Patients are followed at days 7, 14, 21, 100 and 180 after PBSC transplantation, every 6 months for 3 years, and then annually thereafter.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

DISEASE CHARACTERISTICS:
Biopsy-proven diagnosis of high-grade (small noncleaved cell lymphoma [SNCCL] or immunoblastic lymphoma) or intermediate-grade non-Hodgkin lymphoma (NHL) including mantle cell lymphoma (MCL)
SNCCL patients with all of the following factors at presentation of disease:
- Lactate dehydrogenase (LDH) > 500 IU/L
- Unresectable bulky mass > 10 cm
- Stage IV disease with bone marrow involvement
MCL Patients with stage IV disease or in International Prognostic Index (IPI) high- or high-intermediate-risk group at the time of diagnosis
Considered at diagnosis to be high- (3 risk factors) or high-intermediate-risk (2 risk factors) based on an age-adjusted IPI
Poor prognostic factors at diagnosis include stage III or IV disease, lactate dehydrogenase (LDH) level above normal, or ECOG performance status (PS) 2-4
Patients with primary mediastinal large cell lymphoma with or without sclerosis who at diagnosis had elevated LDH level with bulky mediastinal mass > 10 cm associated with a pleural effusion on chest radiography or computer tomography, or who have persistent mediastinal mass with positive disease by post-treatment gallium GA 67 scan
Must have attained a complete response or partial response to first-line standard conventional chemotherapy
ECOG PS 0-1 OR Karnofsky PS 80-100%
Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
FEV_1 > 65% of predicted measurement or DLCO ≥ 45% of predicted measurement
Cardiac ejection fraction > 50% by echocardiogram
Bilirubin ≤ 1.5 x normal
SGOT or SGPT ≤ 2 x normal

Exclusion Criteria

Evidence of lymphoma or < 10% lymphomatous involvement of bone by bilateral bone marrow aspiration and biopsy
Abnormal cytogenetic study of bone marrow aspirate sample NOTE: A new classification scheme for adult non-Hodgkin 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.
Positive HIV antibody
Prior malignancies except for adequately treated basal cell or squamous cell carcinoma of the skin
Hepatitis B surface antigen positivity
Prior bone marrow transplantation

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior bone marrow transplantation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Irradiation in conditioning	total-body irradiation	total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Carmustine in conditioning	peripheral blood stem cell transplantation	Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Irradiation in conditioning	etoposide	total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Irradiation in conditioning	peripheral blood stem cell transplantation	total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Irradiation in conditioning	G-CSF	total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Irradiation in conditioning	cyclophosphamide	total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Carmustine in conditioning	autologous hematopoietic stem cell transplantation	Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Irradiation in conditioning	autologous hematopoietic stem cell transplantation	total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Carmustine in conditioning	carmustine	Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Carmustine in conditioning	etoposide	Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Carmustine in conditioning	cyclophosphamide	Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Carmustine in conditioning	G-CSF	Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation

Primary Outcome Measures

Name	Time	Method
Progression	Assessed at date of progression post-transplant	Event will be recorded if it occurs any time post-transplant, until date of death, last recorded contact, or end-of-study; whichever comes first. Below is reported Progression-free Survival: event is relapse or progression, or death.
Mortality	Assessed at date of death post-transplant	Event will be recorded if it occurs any time from the date of transplant until the end-of-study date, or the date of last contact, whichever comes first.

Secondary Outcome Measures

Name	Time	Method
Short-term and Long-term Treatment-related Toxicities	Any time after transplant	Patient may be assessed for toxicities any time after transplant, up to death, last contact date, or end-of-study date.

Trial Locations

Locations (2): Good Samaritan Regional Medical Center
🇺🇸
Phoenix, Arizona, United States
City of Hope National Medical Center--Main Campus
🇺🇸
Duarte, California, United States
Good Samaritan Regional Medical Center
🇺🇸Phoenix, Arizona, United States