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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00345865
First received: June 28, 2006
Last updated: May 15, 2014
Last verified: May 2014
  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
Drug: Cytarabine
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:


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/milliliter.

  • 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: 300
Study Start Date: August 2005
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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

  Hide 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.

  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

    • 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
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, see Learn About Clinical Studies.

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:
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: May 15, 2014
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:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Carmustine
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014