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

NCT ID: NCT00345865

Last Updated: 2020-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 473 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-24
• Study Completion Date: 2019-06-28

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NHL with irradiation

Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

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.

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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.

irradiation therapy

Intervention Type: RADIATION

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

HL without irradiation

Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.

Group Type: EXPERIMENTAL

carmustine

Intervention Type: DRUG

Day -6, 300 mg/m\^2 over 2 hour

cyclophosphamide

Intervention Type: DRUG

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.

etoposide

Intervention Type: DRUG

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.

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

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.

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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.

irradiation therapy

Intervention Type: RADIATION

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

NHL - HIV infected without irradiation

Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.

Group Type: EXPERIMENTAL

carmustine

Intervention Type: DRUG

Day -6, 300 mg/m\^2 over 2 hour

cyclophosphamide

Intervention Type: DRUG

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.

etoposide

Intervention Type: DRUG

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.

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

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).

Group Type: EXPERIMENTAL

carmustine

Intervention Type: DRUG

Day -6, 300 mg/m\^2 over 2 hour

etoposide

Intervention Type: DRUG

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.

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

Cytarabine

Intervention Type: DRUG

100 mg/m\^2 over one hour BID on days -6 through -2 of BEAM conditioning regimen.

Interventions

carmustine

Day -6, 300 mg/m\^2 over 2 hour

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

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.

Intervention Type: RADIATION

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.

Intervention Type: BIOLOGICAL

Cytarabine

100 mg/m\^2 over one hour BID on days -6 through -2 of BEAM conditioning regimen.

Intervention Type: DRUG

Other Intervention Names

BNCU; Cytoxan; VP-16; PBSC; filgrastim; Ara-C; cytosine arabinoside; Cytosar-U; Depocyt

Eligibility 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

• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Veronika Bachanova, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UMN-0508M72589

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-MT2004-24

Identifier Type: OTHER

Identifier Source: secondary_id

2005LS048

Identifier Type: -

Identifier Source: org_study_id