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

Purpose

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	Intervention	Phase
Lymphoma	Drug: carmustine Drug: cyclophosphamide Drug: etoposide Procedure: peripheral blood stem cell transplantation Radiation: irradiation therapy Biological: G-CSF	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Autologous Peripheral Blood Stem Cell Transplant for Patients With Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer HIV/AIDS Hodgkin Disease Lymphoma

Drug Information available for: Cyclophosphamide Carmustine Etoposide Etoposide phosphate Filgrastim Granulocyte colony-stimulating factor

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Percentage of patients achieving complete response [ Time Frame: Day 100, 1 Year, 2 Years ] [ Designated as safety issue: No ]
response rate uses standard definition

Secondary Outcome Measures:

Prospective validation of the previously published formula used to estimate targeted collection of PBSC [ Time Frame: At end of study ] [ Designated as safety issue: No ]
Outcome will be descriptive in nature.
Immune reconstitution post-transplant in HIV-positive patients compared to HIV-negative patients [ Time Frame: At end of study ] [ Designated as safety issue: No ]
Outcome will be descriptive in nature.
Time to hematopoietic recovery after transplantation [ Time Frame: Days (range) ] [ Designated as safety issue: No ]
return to ANC (absolute neutrophil count) more than 500 cells/millileter.
Duration of response [ Time Frame: At end of study ] [ Designated as safety issue: No ]
median calculation measured in months (range)
Progression-free and overall survival [ Time Frame: 1 Year, 3 Years and 5 Years ] [ Designated as safety issue: No ]
Includes those patients whose disease does not progress, and those alive at specified timeframes.

Estimated Enrollment:	150
Study Start Date:	November 2005
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: NHL With Radiation 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 NHL or 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 without 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 / HL Without Radiation Patients with non Hodgkin's lymphoma or 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 1 hour Other Name: BNCU Drug: cyclophosphamide NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days NHL or 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 Days -6 through -4, 150 mg/m^2 intravenously over 4 hours every 12 hours for 6 total doses. 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 without 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

Arms

Assigned Interventions

Experimental: NHL With Radiation

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 NHL or 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 without 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 / HL Without Radiation

Patients with non Hodgkin's lymphoma or 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 1 hour

Other Name: BNCU

Drug: cyclophosphamide

NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days NHL or 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

Days -6 through -4, 150 mg/m^2 intravenously over 4 hours every 12 hours for 6 total doses.

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 without 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

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 7 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 5 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): Patients receive cyclophosphamide IV over 2 hours on days -6 to -3, carmustine IV over 1 hour 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.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
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
- 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
Patients may be transplanted under this protocol using a syngeneic (identical) twin donor.

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00345865

Contacts

Contact: Timothy Krepski

612-273-2800

tkrepsk1@fairview.org

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Veronika Bachanova, MD

Masonic Cancer Center, University of Minnesota

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00345865 History of Changes
Other Study ID Numbers:	2005LS048, UMN-0508M72589, UMN-MT2004-24
Study First Received:	June 28, 2006
Last Updated:	November 6, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:

Hodgkin lymphoma
non-Hodgkin lymphoma
HIV-associated lymphoma

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Cyclophosphamide
Etoposide phosphate
Etoposide

Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 24, 2013