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Autologous Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), October 2008
Sponsors and Collaborators: Masonic Cancer Center, University of Minnesota
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00345865
  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
Leukemia
Lymphoma
Drug: carboplatin
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Drug: filgrastim
Drug: ifosfamide
Drug: rituximab
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: radiation therapy
Procedure: total-body irradiation
Phase II

MedlinePlus related topics: AIDS Cancer Fungal Infections Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma
Drug Information available for: Ifosfamide Cyclophosphamide Carboplatin Filgrastim Etoposide Carmustine Rituximab Etoposide phosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Autologous Peripheral Blood Stem Cell Transplant for Patients With Lymphoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percentage of patients achieving complete response [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Progression-free and overall survival [ Designated as safety issue: No ]
  • Safety and outcome of autologous peripheral blood stem cell (PBSC) transplant in the management of lymphoma in HIV-positive patients with an adequate control of HIV disease [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Prospective validation of the previously published formula used to estimate targeted collection of PBSC [ Designated as safety issue: No ]
  • Immune reconstitution post-transplant in HIV-positive patients compared to HIV-negative patients [ Designated as safety issue: No ]
  • Time to hematopoietic recovery after transplantation [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: November 2005
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
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 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 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Non-Hodgkin's lymphoma (NHL) of 1 of the following subtypes:

      • Precursor B-cell or precursor T-cell NHL

        • Lymphoblastic lymphoma in second or greater complete remission (CR) or first or subsequent PR OR lymphoblastic lymphoma in first CR (CR1) with high-risk features (i.e., stage IV disease, lactic dehydrogenase [LDH] > 2 times normal, or 2 or more extranodal sites)
      • Mature B-cell lymphoma, including any of the following:

        • Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) in ≥ CR1 with molecularly negative disease* NOTE: *Patients in CR with molecularly positive disease or in PR are not eligible
        • Follicular lymphoma in ≥ CR1 or first PR (PR1) (if treatment is delayed until clinically required) OR in ≥ second CR/PR (CR2/PR2) and was treated at diagnosis (without clinical symptoms necessitating treatment, such as B symptoms, bulky disease, marrow or other organ compromise)
        • Diffuse large B-cell lymphoma in ≥ CR2 or ≥ PR1 OR in CR1 with high-intermediate or high International Prognostic Index (IPI) score (≥ 2 for age-adjusted IPI or ≥ 3 for IPI) at diagnosis
        • Mantle cell lymphoma in first or greater CR or PR
        • Burkitt's/Burkitt's-like lymphoma in CR1 after receiving initial therapy (except patients with localized** lymphoma) OR in PR and failed to achieve CR NOTE: **Localized (stage I or Ziegler stage A) disease allowed only if failed to achieve CR1 or in relapse
      • Mature T-cell lymphoma, including any of the following:

        • Primary T-cell lymphoma not otherwise specified, angioimmunoblastic lymphoma, or ALK-positive anaplastic large cell lymphoma that was previously treated with initial therapy (may or may not be in CR)
        • Mycosis fungoides/Sezary syndrome in ≥ CR2/PR2
      • No resistant or refractory lymphoma (i.e., no partial remission [PR] after treatment with up to 3 courses of combination chemotherapy)
    • Hodgkin's lymphoma (HL) meeting the following criteria:

      • Failed prior therapy
      • No resistant disease (initial disease or at relapse)

        • Resistant disease is defined as failing to achieve an objective PR to 3 courses of combination noncross-resistant chemotherapy
      • Patients with stage I or II disease treated with primary radiation must have failed (no CR OR progression after CR) ≥ 1 salvage combination chemotherapy regimen
      • Patients with advanced (stage III or IV) disease must have failed a doxorubicin hydrochloride-containing regimen (e.g., doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine [ABVD]) or an alternative noncross-resistant chemotherapy regimen (e.g., mechlorethamine, vincristine, procarbazine hydrochloride, and prednisone [MOPP])
      • High-risk disease allowed, including any of the following:

        • Failed to achieve CR with initial combination chemotherapy
        • Bulky disease after initial therapy (chemotherapy or radiation), defined as residual mediastinal mass ≥ 5 cm or other residual mass ≥ 10 cm accompanied by other features of persisting disease (e.g., gallium or positron-emission tomography [PET] scan positive; high LDH; enlarging mass on serial x-rays or biopsy-positive)
  • Bone marrow cellularity > 20% with < 10% involvement with tumor
  • History of CNS involvement by lymphoma or relapsed primary CNS lymphoma allowed
  • Active CNS disease allowed if standard treatment for CNS lymphoma was completed and there is no evidence of progressive CNS disease at study entry
  • Patients with lymphoma who are HIV positive are eligible as long as all of the following criteria are met:

    • Must be on maximally active anti-HIV regimen to control disease
    • CD4+ ≥ 50/μL
    • HIV RNA viral load ≤ 100,000 copies/mL on each sample 4 weeks apart

      • Most recent level must have been within the past month
  • No chemotherapy-resistant disease
  • Ineligible for any higher priority transplant protocols

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 90-100% (70-100% if poor performance status is related to lymphoma)
  • Life expectancy > 8 weeks
  • WBC > 2,500/mm³
  • Absolute neutrophil count > 1,500/mm³
  • Platelet count > 100,000/mm³ (without transfusion)
  • Hemoglobin > 8 g/dL (without transfusion)
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
  • Bilirubin ≤ 2.0 mg/dL
  • AST< 5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 5 times ULN
  • No uncontrolled cardiac disease, including unstable angina, decompensated congestive heart failure, or arrhythmia
  • LVEF > 45% by MUGA
  • No significant obstructive airway disease (FEV_1 ≥ 50%)
  • Corrected DLCO > 50% of predicted
  • No severe prior or ongoing chronic liver disease
  • No serious uncontrolled infection
  • No other evidence of serious organ dysfunction that is not attributable to tumor
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Hepatitis B carriers allowed

    • No rituximab as part of study chemotherapy mobilization

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 14 days since prior epoetin alfa
  • At least 21 days since prior darbepoetin alfa or pegfilgrastim
  • At least 10 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00345865

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: Marcie Tomblyn, MD, MS Masonic Cancer Center, University of Minnesota
  More Information

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

Responsible Party: Masonic Cancer Center at University of Minnesota ( Marcie Tomblyn )
Study ID Numbers: CDR0000483183, UMN-2005LS048, UMN-0508M72589, UMN-MT2004-24
Study First Received: June 28, 2006
Last Updated: October 24, 2008
ClinicalTrials.gov Identifier: NCT00345865  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
HIV-associated Hodgkin lymphoma
AIDS-related diffuse large cell lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related lymphoblastic lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
AIDS-related small noncleaved cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
stage I adult Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage II childhood Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent mycosis fungoides/Sezary syndrome
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma

Study placed in the following topic categories:
Sezary syndrome
Lymphoma, Mantle-Cell
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Central nervous system lymphoma, primary
Mycoses
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Etoposide
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Acquired Immunodeficiency Syndrome
Carmustine
Carboplatin
HIV Infections
Hodgkin lymphoma, childhood
Anaplastic large cell lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Leukemia, Lymphoid
Hodgkin's disease
Cutaneous T-cell lymphoma
Lymphoma, Follicular
Sezary Syndrome

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 13, 2009