Autologous Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00345865

Recruitment Status : Completed

First Posted : June 29, 2006

Results First Posted : July 14, 2020

Last Update Posted : July 14, 2020

Sponsor:

Information provided by (Responsible Party):

Masonic Cancer Center, University of Minnesota

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: carmustine Drug: cyclophosphamide Drug: etoposide Procedure: peripheral blood stem cell transplantation Radiation: irradiation therapy Biological: G-CSF Drug: Cytarabine	Phase 2

Show detailed description

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.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	473 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Autologous Peripheral Blood Stem Cell Transplant for Patients With Lymphoma
Actual Study Start Date :	August 24, 2005
Actual Primary Completion Date :	June 28, 2019
Actual Study Completion Date :	June 28, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Hodgkin Lymphoma Lymphoma AIDS Related

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: NHL with irradiation Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF.	Drug: cyclophosphamide NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days. HL without radiation: Cyclophosphamide, Days - 6 through -3, 1.5 gm/m^2 over 2 hours daily x 4 days. Cyclophosphamide will be dosed based on actual body weight (ABW) unless the patient is 20% or more of ideal body weight (IBW). If more than 20% of ideal body weight, an adjusted ideal body weight (AIBW) will be used for dosing. Other Name: Cytoxan Procedure: peripheral blood stem cell transplantation Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF alone (filgrastim) or using ifosfamide/carboplatin/etoposide and with or without rituximab. Leukapheresis is to begin on Day 5. Other Name: PBSC Radiation: irradiation therapy Patients undergo total body irradiation (TBI) twice daily on days -4 to -1. > 1000 cGy to whole lung, kidney, or abdominal bath. > 3000 cGy to spinal cord, myocardium, mediastinum, lumbar periaortic lymph nodes. > 3600 cGy to whole brain. Biological: G-CSF Day 5: Begin G-CSF 5μg/kg/day subcutaneously (SQ) rounded to the nearest vial size. Continue G-CSF until absolute neutrophil count (ANC) > 1500/μl x 3 consecutive days. If ANC falls <1000/μL, restart G-CSF. Other Name: filgrastim
Experimental: HL without irradiation Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.	Drug: carmustine Day -6, 300 mg/m^2 over 2 hour Other Name: BNCU Drug: cyclophosphamide NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days. HL without radiation: Cyclophosphamide, Days - 6 through -3, 1.5 gm/m^2 over 2 hours daily x 4 days. Cyclophosphamide will be dosed based on actual body weight (ABW) unless the patient is 20% or more of ideal body weight (IBW). If more than 20% of ideal body weight, an adjusted ideal body weight (AIBW) will be used for dosing. Other Name: Cytoxan Drug: etoposide NHL without radiation and cyclophosphamide: Etoposide 100 mg/m2 IV over 2 hours twice daily on Day -5 through -2. HL without radiation: 150 mg/m^2 intravenously over 4 hours every 12 hours for 6 total doses on Days -6 through -4. Other Name: VP-16 Procedure: peripheral blood stem cell transplantation Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF alone (filgrastim) or using ifosfamide/carboplatin/etoposide and with or without rituximab. Leukapheresis is to begin on Day 5. Other Name: PBSC Biological: G-CSF Day 5: Begin G-CSF 5μg/kg/day subcutaneously (SQ) rounded to the nearest vial size. Continue G-CSF until absolute neutrophil count (ANC) > 1500/μl x 3 consecutive days. If ANC falls <1000/μL, restart G-CSF. Other Name: filgrastim
Experimental: NHL - HIV infected with irradiation Non Hodgkin's Lymphoma patients infected with HIV, treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF.	Drug: cyclophosphamide NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days. HL without radiation: Cyclophosphamide, Days - 6 through -3, 1.5 gm/m^2 over 2 hours daily x 4 days. Cyclophosphamide will be dosed based on actual body weight (ABW) unless the patient is 20% or more of ideal body weight (IBW). If more than 20% of ideal body weight, an adjusted ideal body weight (AIBW) will be used for dosing. Other Name: Cytoxan Procedure: peripheral blood stem cell transplantation Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF alone (filgrastim) or using ifosfamide/carboplatin/etoposide and with or without rituximab. Leukapheresis is to begin on Day 5. Other Name: PBSC Radiation: irradiation therapy Patients undergo total body irradiation (TBI) twice daily on days -4 to -1. > 1000 cGy to whole lung, kidney, or abdominal bath. > 3000 cGy to spinal cord, myocardium, mediastinum, lumbar periaortic lymph nodes. > 3600 cGy to whole brain. Biological: G-CSF Day 5: Begin G-CSF 5μg/kg/day subcutaneously (SQ) rounded to the nearest vial size. Continue G-CSF until absolute neutrophil count (ANC) > 1500/μl x 3 consecutive days. If ANC falls <1000/μL, restart G-CSF. Other Name: filgrastim
Experimental: NHL - HIV infected without irradiation Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.	Drug: carmustine Day -6, 300 mg/m^2 over 2 hour Other Name: BNCU Drug: cyclophosphamide NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days. HL without radiation: Cyclophosphamide, Days - 6 through -3, 1.5 gm/m^2 over 2 hours daily x 4 days. Cyclophosphamide will be dosed based on actual body weight (ABW) unless the patient is 20% or more of ideal body weight (IBW). If more than 20% of ideal body weight, an adjusted ideal body weight (AIBW) will be used for dosing. Other Name: Cytoxan Drug: etoposide NHL without radiation and cyclophosphamide: Etoposide 100 mg/m2 IV over 2 hours twice daily on Day -5 through -2. HL without radiation: 150 mg/m^2 intravenously over 4 hours every 12 hours for 6 total doses on Days -6 through -4. Other Name: VP-16 Procedure: peripheral blood stem cell transplantation Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF alone (filgrastim) or using ifosfamide/carboplatin/etoposide and with or without rituximab. Leukapheresis is to begin on Day 5. Other Name: PBSC Biological: G-CSF Day 5: Begin G-CSF 5μg/kg/day subcutaneously (SQ) rounded to the nearest vial size. Continue G-CSF until absolute neutrophil count (ANC) > 1500/μl x 3 consecutive days. If ANC falls <1000/μL, restart G-CSF. Other Name: filgrastim
Experimental: NHL without radiation and cyclosporine 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).	Drug: carmustine Day -6, 300 mg/m^2 over 2 hour Other Name: BNCU Drug: etoposide NHL without radiation and cyclophosphamide: Etoposide 100 mg/m2 IV over 2 hours twice daily on Day -5 through -2. HL without radiation: 150 mg/m^2 intravenously over 4 hours every 12 hours for 6 total doses on Days -6 through -4. Other Name: VP-16 Procedure: peripheral blood stem cell transplantation Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF alone (filgrastim) or using ifosfamide/carboplatin/etoposide and with or without rituximab. Leukapheresis is to begin on Day 5. Other Name: PBSC Biological: G-CSF Day 5: Begin G-CSF 5μg/kg/day subcutaneously (SQ) rounded to the nearest vial size. Continue G-CSF until absolute neutrophil count (ANC) > 1500/μl x 3 consecutive days. If ANC falls <1000/μL, restart G-CSF. Other Name: filgrastim Drug: Cytarabine 100 mg/m^2 over one hour BID on days -6 through -2 of BEAM conditioning regimen. Other Names: Ara-C cytosine arabinoside Cytosar-U Depocyt

Outcome Measures

Primary Outcome Measures :

Number of Participants With 1 Year Progression Free Survival [ Time Frame: 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 2 Years Progression Free Survival [ Time Frame: 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 Overall Survival [ Time Frame: 1 year ]
Number of Participants With 2 Years Overall Survival [ Time Frame: 2 years ]

Secondary Outcome Measures :

Number of Participants With Hematopoietic Recovery After Transplantation [ Time Frame: Day 42 ]
return to ANC (absolute neutrophil count) more than 500 cells/milliliter.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	up to 75 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

Patients eligible for any higher priority transplant protocols
Women who are pregnant or breast feeding
Patients with chemotherapy resistant disease

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00345865

Locations

Layout table for location information

United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Layout table for investigator information

Principal Investigator:	Veronika Bachanova, MD	Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

Documents provided by Masonic Cancer Center, University of Minnesota:

Study Protocol and Statistical Analysis Plan [PDF] January 16, 2014

More Information

Layout table for additonal information

Responsible Party:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00345865
Other Study ID Numbers:	2005LS048 UMN-0508M72589 ( Other Identifier: IRB, University of Minnesota ) UMN-MT2004-24 ( Other Identifier: Blood and Marrow Transplantation Program )
First Posted:	June 29, 2006 Key Record Dates
Results First Posted:	July 14, 2020
Last Update Posted:	July 14, 2020
Last Verified:	July 2020

Keywords provided by Masonic Cancer Center, University of Minnesota:


Hodgkin lymphoma non-Hodgkin lymphoma HIV-associated lymphoma

Additional relevant MeSH terms:

Layout table for MeSH terms

Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Cyclophosphamide Carmustine Etoposide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs	Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents

To Top