Autologous Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Procedure: peripheral blood stem cell transplantationRadiation: irradiation therapyBiological: G-CSF
- Registration Number
- NCT00345865
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as ifosfamide, etoposide, and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored for peripheral stem cell transplant. Giving more chemotherapy, such as cyclophosphamide, carmustine, and etoposide, and total-body irradiation prepares the patient's bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. More radiation therapy is given after transplant to kill any remaining cancer cells.
PURPOSE: This phase II trial is studying how well autologous peripheral stem cell transplant works in treating patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* Determine the disease-free survival and overall survival of patients with non-Hodgkin's or Hodgkin's lymphoma treated with autologous peripheral blood stem cell transplantation (PBSCT).
* Verify the safety and efficacy of autologous PBSCT in patients with HIV disease and relapsed lymphoma.
Secondary
* Evaluate immune reconstitution in HIV-positive patients undergoing autologous PBSCT and compare to immune reconstitution in HIV-negative patients.
* Predict the adequacy of peripheral blood stem cell (PBSC) harvest prior to flow analysis of a PBSC yield.
* Determine the time to engraftment for neutrophils and platelets.
OUTLINE:
* Peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) alone: Patients not requiring further disease reduction receive G-CSF subcutaneously (SC) once daily on days 1-8. Patients undergo PBSC collection by leukapheresis on days 5-8. Patients who do not adequately mobilize with G-CSF alone proceed to chemo-mobilization.
* Chemo-mobilization: Patients requiring further disease reduction receive 1 of 2 chemo-mobilization regimens.
* Patients with CD20+ non-Hodgkin's lymphoma (NHL) or lymphocyte predominant Hodgkin's lymphoma: Patients receive rituximab intravenously (IV) over 6-8 hours on day 1, ifosfamide IV over 2 hours and etoposide IV over 30 minutes on days 2-4, and carboplatin IV over 1 hour on day 2. Patients receive G-CSF SC once daily beginning on day 5 and continuing until leukapheresis is completed. Patients undergo PBSC collection by leukapheresis on days 12-15.
* All other patients: Patients receive ifosfamide IV over 2 hours and etoposide IV over 30 minutes on days 1-3 and carboplatin IV over 1 hour on day 1. Patients receive G-CSF SC once daily beginning on day 4 and continuing until leukapheresis is completed. Patients undergo PBSC collection by leukapheresis on days 12-15.
* Autologous PBSC transplantation (PBSCT) (Patients with NHL undergoing irradiation): Patients receive cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total body irradiation (TBI) twice daily on days -4 to -1. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.
* Autologous PBSCT (Patients with Hodgkin's lymphoma or NHL not undergoing irradiation and cyclophosphamide): Patients receive camustine IV over 2 hours on days -6, etoposide IV over 2 hours twice daily on days -5 to -2, and melphalan over 1 hour on day -1. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.
* Autologous PBSC transplantation (PBSCT) (Patients with HL not undergoing irradiation): Patients receive cyclophosphamide IV over 2 hours on days -6 to -3, camustine IV over 2 hours on day -6, and etoposide IV over 4 hours twice daily on days -6 to -4. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.
* Post-transplant irradiation: Patients undergo post-transplant irradiation beginning on day 28. Persisting nodal masses ≥ 2 cm are treated with additional localized external beam irradiation.
* Post-transplant Rituximab therapy: patients with CD20+ NHL may undergo Rituximab maintenance starting between day +45 and +90 and being repeated at day +180 ± 14 days.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 473
-
Karnofsky performance status: >80% (>60% if poor performance status is related to lymphoma)
-
No evidence of serious organ dysfunction that is not attributable to tumor
- Central nervous system: Patients with a history of CNS involvement by lymphoma or with relapsed primary lymphoma will be eligible.
- Infection: Patients with serious uncontrolled infections at the time of transplant will be excluded.
-
Hepatitis B: Patients who are carriers of Hepatitis B will be included in this study. These patients are not eligible to receive rituximab as a component of their chemotherapy mobilization.
-
HIV disease. Patients with HIV disease are eligible for this study provided that:
- Patients will be seen in the infectious disease (ID)/HIV clinic prior to enrollment on study for the purpose of determining eligibility and for local coordination of HIV care during the peri-transplant period.
- Must be on a maximally active anti-HIV regimen
- CD4+ ≥ 50/μL
- HIV RNA viral load ≤ 100,000 copies per mL on each of samples 4 weeks apart. The most recent level must be within one month of enrollment.
-
Non-Hodgkin's lymphoma (NHL). Patients with chemo-sensitive histologically confirmed NHL.
-
Precursor B-cell or Precursor T-cell NHL
-
Lymphoblastic lymphoma
- All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
-
-
Mature B-cell Lymphomas:
- Small lymphocytic lymphoma (SLL) or Chronic Lymphocytic Leukemia (CLL)
- Follicular Lymphoma
- Diffuse Large B-cell Lymphoma
- Mantle Cell Lymphoma
- Burkitt's/Burkitt's like
-
Mature T-cell lymphoma
-
-
Hodgkin's lymphoma (HL)
- patients with histologically proven HL will be eligible for transplantation after failing prior therapy.
- Patients eligible for any higher priority transplant protocols
- Women who are pregnant or breast feeding
- Patients with chemotherapy resistant disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NHL with irradiation G-CSF Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. HL without irradiation G-CSF Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected with irradiation G-CSF Non Hodgkin's Lymphoma patients infected with HIV, treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. NHL with irradiation peripheral blood stem cell transplantation Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. NHL with irradiation irradiation therapy Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected with irradiation peripheral blood stem cell transplantation Non Hodgkin's Lymphoma patients infected with HIV, treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected with irradiation irradiation therapy Non Hodgkin's Lymphoma patients infected with HIV, treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected without irradiation peripheral blood stem cell transplantation Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected without irradiation G-CSF Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. HL without irradiation peripheral blood stem cell transplantation Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL without radiation and cyclosporine peripheral blood stem cell transplantation Patients with non Hodgkin's lymphoma ineligible to receive total body irradiation because of prior radiation and are not candidates for high dose cyclophosphamide will be treated with carmustine, etoposide, cytarabine, and melphalan followed by peripheral blood stem cell transplantation and G-CSF (called BEAM conditioning). NHL without radiation and cyclosporine G-CSF Patients with non Hodgkin's lymphoma ineligible to receive total body irradiation because of prior radiation and are not candidates for high dose cyclophosphamide will be treated with carmustine, etoposide, cytarabine, and melphalan followed by peripheral blood stem cell transplantation and G-CSF (called BEAM conditioning). NHL with irradiation cyclophosphamide Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. HL without irradiation carmustine Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. HL without irradiation etoposide Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. HL without irradiation cyclophosphamide Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected with irradiation cyclophosphamide Non Hodgkin's Lymphoma patients infected with HIV, treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected without irradiation carmustine Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected without irradiation cyclophosphamide Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL - HIV infected without irradiation etoposide Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF. NHL without radiation and cyclosporine carmustine Patients with non Hodgkin's lymphoma ineligible to receive total body irradiation because of prior radiation and are not candidates for high dose cyclophosphamide will be treated with carmustine, etoposide, cytarabine, and melphalan followed by peripheral blood stem cell transplantation and G-CSF (called BEAM conditioning). NHL without radiation and cyclosporine etoposide Patients with non Hodgkin's lymphoma ineligible to receive total body irradiation because of prior radiation and are not candidates for high dose cyclophosphamide will be treated with carmustine, etoposide, cytarabine, and melphalan followed by peripheral blood stem cell transplantation and G-CSF (called BEAM conditioning). NHL without radiation and cyclosporine Cytarabine Patients with non Hodgkin's lymphoma ineligible to receive total body irradiation because of prior radiation and are not candidates for high dose cyclophosphamide will be treated with carmustine, etoposide, cytarabine, and melphalan followed by peripheral blood stem cell transplantation and G-CSF (called BEAM conditioning).
- Primary Outcome Measures
Name Time Method Number of Participants With 2 Years Progression Free Survival 2 years Progression is determined using Response Criteria for Non-Hodgkin's Lymphoma given by NCI Sponsored International Working Group.
Definition is as follows:
At least a 50% increase from nadir of any previously identified abnormal node. Appearance of any new lesion during or at the end of therapy.Number of Participants With 1 Year Progression Free Survival 1 year Progression is defined using the Response Criteria for Non-Hodgkin's Lymphoma given by NCI Sponsored International Working Group.The definition is as follows:
At least a 50% increase from nadir of any previously identified abnormal node. Appearance of any new lesion during or at the end of therapy.Number of Participants With 1 Year Overall Survival 1 year Number of Participants With 2 Years Overall Survival 2 years
- Secondary Outcome Measures
Name Time Method Number of Participants With Hematopoietic Recovery After Transplantation Day 42 return to ANC (absolute neutrophil count) more than 500 cells/milliliter.
Trial Locations
- Locations (1)
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States