Lymphoma
Conditions
Keywords
stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV mantle cell lymphoma, stage III mantle cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma
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.
Interventions
DRUGcarmustine
Unique to the Carmustine in Conditioning arm
DRUGcyclophosphamide
Used in Both Arms
DRUGetoposide
Used in Both Arms
PROCEDUREautologous hematopoietic stem cell transplantation
Both arms are given autologous stem cell transplantation
PROCEDUREperipheral blood stem cell transplantation
Both arms are given peripheral blood stem cell transplantation (Peripheral blood stem cells are the material, autologous transplant is the modality).
RADIATIONtotal-body irradiation
Unique to the Radiation in Conditioning Arm
DRUGG-CSF
G-CSF is given in both treatment arms, both to mobilize stem cells before apheresis, and to promote recovery of granulocytes after stem-cell re-infusion.
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 59 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Irradiation in Conditioning total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor
cyclophosphamide
etoposide
autologous hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
G-CSF | 55 |
| Carmustine in Conditioning Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor
carmustine
cyclophosphamide
etoposide
autologous hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
G-CSF | 5 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 9 | 0 |
Baseline characteristics
| Characteristic | Irradiation in Conditioning | Carmustine in Conditioning | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 5 Participants | 60 Participants |
| Age, Continuous | 44.2 years | 32.4 years | 42.5 years |
| Region of Enrollment United States | 55 participants | 5 participants | 60 participants |
| Sex: Female, Male Female | 22 Participants | 3 Participants | 25 Participants |
| Sex: Female, Male Male | 33 Participants | 2 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 39 / 55 | 1 / 5 |
| serious Total, serious adverse events | 0 / 55 | 0 / 5 |
Outcome results
Primary
Mortality
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.
Time frame: Assessed at date of death post-transplant
Population: per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irradiation in Conditioning | Mortality | 19 participants |
| Carmustine in Conditioning | Mortality | 1 participants |
Comparison: Phase II analysis: There was no power calculation.p-value: 0.6995% CI: [0.09, 4.99]Regression, Cox
Primary
Progression
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.
Time frame: Assessed at date of progression post-transplant
Population: per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irradiation in Conditioning | Progression | 22 participants |
| Carmustine in Conditioning | Progression | 1 participants |
Comparison: There is no power calculation as this is a phase II study. This is an Event-free Survival, in which an event can be Relapse/Progression, or Death. Censoring can be at the End of follow-up date, or at the End of study date.p-value: 0.5195% CI: [0.07, 3.79]Regression, Cox
Secondary
Short-term and Long-term Treatment-related Toxicities
Patient may be assessed for toxicities any time after transplant, up to death, last contact date, or end-of-study date.
Time frame: Any time after transplant
Population: per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irradiation in Conditioning | Short-term and Long-term Treatment-related Toxicities | 39 participants |
| Carmustine in Conditioning | Short-term and Long-term Treatment-related Toxicities | 1 participants |