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

Autologous Peripheral Blood Stem Cell Transplant for Patients With Lymphoma

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00345865
Enrollment
473
Registered
2006-06-29
Start date
2005-08-24
Completion date
2019-06-28
Last updated
2020-07-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Keywords

Hodgkin lymphoma, non-Hodgkin lymphoma, HIV-associated lymphoma

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.

Interventions

DRUGcarmustine

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

DRUGcyclophosphamide

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.

DRUGetoposide

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.

PROCEDUREperipheral 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.

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.

BIOLOGICALG-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.

DRUGCytarabine

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

Sponsors

Masonic Cancer Center, University of Minnesota
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With 1 Year Progression Free Survival1 yearProgression 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 Survival2 yearsProgression 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 Survival1 year
Number of Participants With 2 Years Overall Survival2 years

Secondary

MeasureTime frameDescription
Number of Participants With Hematopoietic Recovery After TransplantationDay 42return to ANC (absolute neutrophil count) more than 500 cells/milliliter.

Countries

United States

Participant flow

Participants by arm

ArmCount
NHL With Irradiation
Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF.
171
HL Without Irradiation
Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.
149
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.
2
NHL - HIV Infected Without Irradiation
Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.
5
NHL Without Radiation and Cyclophosphamide
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).
146
Total473

Baseline characteristics

CharacteristicNHL With IrradiationHL Without IrradiationNHL - HIV Infected With IrradiationNHL - HIV Infected Without IrradiationNHL Without Radiation and CyclophosphamideTotal
Age, Categorical
<=18 years
4 Participants13 Participants0 Participants0 Participants0 Participants17 Participants
Age, Categorical
>=65 years
41 Participants7 Participants0 Participants1 Participants39 Participants88 Participants
Age, Categorical
Between 18 and 65 years
126 Participants129 Participants2 Participants4 Participants107 Participants368 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants
Race (NIH/OMB)
Asian
4 Participants2 Participants0 Participants0 Participants3 Participants9 Participants
Race (NIH/OMB)
Black or African American
10 Participants5 Participants1 Participants0 Participants4 Participants20 Participants
Race (NIH/OMB)
More than one race
1 Participants3 Participants0 Participants0 Participants0 Participants4 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
9 Participants12 Participants0 Participants0 Participants3 Participants24 Participants
Race (NIH/OMB)
White
147 Participants127 Participants1 Participants5 Participants135 Participants415 Participants
Sex: Female, Male
Female
53 Participants74 Participants1 Participants1 Participants54 Participants183 Participants
Sex: Female, Male
Male
118 Participants75 Participants1 Participants4 Participants92 Participants290 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
47 / 1719 / 1491 / 21 / 525 / 146
other
Total, other adverse events
125 / 17198 / 1492 / 22 / 5120 / 146
serious
Total, serious adverse events
34 / 17118 / 1491 / 21 / 50 / 146

Outcome results

Primary

Number of Participants With 1 Year Overall Survival

Time frame: 1 year

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
NHL With IrradiationNumber of Participants With 1 Year Overall Survival139 Participants
HL Without IrradiationNumber of Participants With 1 Year Overall Survival144 Participants
NHL - HIV Infected With IrradiationNumber of Participants With 1 Year Overall Survival1 Participants
NHL - HIV Infected Without IrradiationNumber of Participants With 1 Year Overall Survival5 Participants
NHL Without Radiation and CyclophosphamideNumber of Participants With 1 Year Overall Survival128 Participants
Primary

Number of Participants With 1 Year Progression Free Survival

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.

Time frame: 1 year

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
NHL With IrradiationNumber of Participants With 1 Year Progression Free Survival112 Participants
HL Without IrradiationNumber of Participants With 1 Year Progression Free Survival102 Participants
NHL - HIV Infected With IrradiationNumber of Participants With 1 Year Progression Free Survival1 Participants
NHL - HIV Infected Without IrradiationNumber of Participants With 1 Year Progression Free Survival2 Participants
NHL Without Radiation and CyclophosphamideNumber of Participants With 1 Year Progression Free Survival116 Participants
Primary

Number of Participants With 2 Years Overall Survival

Time frame: 2 years

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
NHL With IrradiationNumber of Participants With 2 Years Overall Survival124 Participants
HL Without IrradiationNumber of Participants With 2 Years Overall Survival140 Participants
NHL - HIV Infected With IrradiationNumber of Participants With 2 Years Overall Survival1 Participants
NHL - HIV Infected Without IrradiationNumber of Participants With 2 Years Overall Survival4 Participants
NHL Without Radiation and CyclophosphamideNumber of Participants With 2 Years Overall Survival121 Participants
Primary

Number of Participants With 2 Years Progression Free Survival

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.

Time frame: 2 years

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
NHL With IrradiationNumber of Participants With 2 Years Progression Free Survival96 Participants
HL Without IrradiationNumber of Participants With 2 Years Progression Free Survival91 Participants
NHL - HIV Infected With IrradiationNumber of Participants With 2 Years Progression Free Survival1 Participants
NHL - HIV Infected Without IrradiationNumber of Participants With 2 Years Progression Free Survival1 Participants
NHL Without Radiation and CyclophosphamideNumber of Participants With 2 Years Progression Free Survival106 Participants
Secondary

Number of Participants With Hematopoietic Recovery After Transplantation

return to ANC (absolute neutrophil count) more than 500 cells/milliliter.

Time frame: Day 42

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
NHL With IrradiationNumber of Participants With Hematopoietic Recovery After Transplantation171 Participants
HL Without IrradiationNumber of Participants With Hematopoietic Recovery After Transplantation147 Participants
NHL - HIV Infected With IrradiationNumber of Participants With Hematopoietic Recovery After Transplantation2 Participants
NHL - HIV Infected Without IrradiationNumber of Participants With Hematopoietic Recovery After Transplantation5 Participants
NHL Without Radiation and CyclophosphamideNumber of Participants With Hematopoietic Recovery After Transplantation145 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026