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Combination Chemotherapy With or Without Total-Body Irradiation Followed By Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00559104
First received: November 15, 2007
Last updated: July 17, 2015
Last verified: July 2015
  Purpose

RATIONALE: Giving chemotherapy and radiation therapy to the entire body before an autologous peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. The patient's stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with or without total-body irradiation followed by a stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Drug: G-CSF
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High-Dose Therapy and Autologous Stem Cell Transplantation During Remission in Poor-Risk Age-Adjusted International Prognostic Index High and High-Intermediate Risk Group Patients With Intermediate Grade and High-Grade Non-Hodgkin's Lymphoma Including Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Progression [ Time Frame: Assessed at date of progression post-transplant ] [ Designated as safety issue: No ]

    Event will be recorded if it occurs any time post-transplant, until date of death, last recorded contact, or end-of-study; whichever comes first.

    Below is reported Progression-free Survival: event is relapse or progression, or death.


  • Mortality [ Time Frame: Assessed at date of death post-transplant ] [ Designated as safety issue: No ]
    Event will be recorded if it occurs any time from the date of transplant until the end-of-study date, or the date of last contact, whichever comes first.


Secondary Outcome Measures:
  • Short-term and Long-term Treatment-related Toxicities [ Time Frame: Any time after transplant ] [ Designated as safety issue: Yes ]
    Patient may be assessed for toxicities any time after transplant, up to death, last contact date, or end-of-study date.


Enrollment: 60
Study Start Date: October 1998
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Irradiation in conditioning
total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation
Drug: cyclophosphamide
Used in Both Arms
Other Name: Cytoxan, CTX
Drug: etoposide
Used in Both Arms
Other Name: VP-16
Procedure: autologous hematopoietic stem cell transplantation
Both arms are given autologous stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Both arms are given peripheral blood stem cell transplantation (Peripheral blood stem cells are the material, autologous transplant is the modality).
Radiation: total-body irradiation
Unique to the Radiation in Conditioning Arm
Drug: G-CSF
G-CSF is given in both treatment arms, both to mobilize stem cells before apheresis, and to promote recovery of granulocytes after stem-cell re-infusion.
Other Name: Granulocyte-colony stimulating factor
Active Comparator: Carmustine in conditioning
Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Drug: carmustine
Unique to the Carmustine in Conditioning arm
Other Name: BCNU
Drug: cyclophosphamide
Used in Both Arms
Other Name: Cytoxan, CTX
Drug: etoposide
Used in Both Arms
Other Name: VP-16
Procedure: autologous hematopoietic stem cell transplantation
Both arms are given autologous stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Both arms are given peripheral blood stem cell transplantation (Peripheral blood stem cells are the material, autologous transplant is the modality).
Drug: G-CSF
G-CSF is given in both treatment arms, both to mobilize stem cells before apheresis, and to promote recovery of granulocytes after stem-cell re-infusion.
Other Name: Granulocyte-colony stimulating factor

Detailed Description:

OBJECTIVES:

  • To evaluate the outcome of patients with poor-risk, age-adjusted International Prognostic Index high- and high-intermediate-risk, intermediate- and high-grade non-Hodgkin lymphoma undergoing high-dose therapy comprising etoposide and cyclophosphamide, either carmustine or total-body irradiation, and autologous stem cell transplantation (ASCT) given as a consolidation therapy.
  • To evaluate the role of high-dose therapy and ASCT during first partial or complete remission (1PR/CR) in patients with poor-risk primary mediastinal large cell lymphoma.
  • To evaluate the role of high-dose therapy and ASCT during first 1PR/CR in patients with advanced-stage mantle cell lymphoma.
  • To evaluate the short-term and long-term toxicities of high-dose therapy and ASCT when performed during 1PR/CR in patients with poor-risk aggressive lymphomas.

OUTLINE: Patients are stratified according to disease (diffuse mixed, diffuse large cell, and immunoblastic lymphoma vs primary mediastinal large cell lymphoma vs small noncleaved cell lymphoma vs stage IV mantle cell lymphoma).

Patients' peripheral blood stem cells (PBSC) are collected after mobilization. A minimum of 2.0 x 10^6 CD34+ cells/kg must be collected. Patients experiencing disease progression during stem cell collection will be removed from study. Patients are assigned to undergo 1 of 2 therapeutic regimens.

  • Regimen 1: Patients undergo total-body irradiation (TBI) on days -8 to -5 and receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous PBSC transplantation on day 0.
  • Regimen 2 (for patients who have received any prior thoracic irradiation or patients who underwent previous irradiation that precludes the use of TBI): Patients receive carmustine IV over 2 hours on days -7 to -5. Patients then receive etoposide and cyclophosphamide and undergo autologous PBSC transplantation as in regimen 1.

Patients with residual bulky disease greater than 5 cm may undergo involved-field radiotherapy before or after transplantation.

Patients are followed at days 7, 14, 21, 100 and 180 after PBSC transplantation, every 6 months for 3 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   16 Years to 59 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DISEASE CHARACTERISTICS:
  • Biopsy-proven diagnosis of high-grade (small noncleaved cell lymphoma [SNCCL] or immunoblastic lymphoma) or intermediate-grade non-Hodgkin lymphoma (NHL) including mantle cell lymphoma (MCL)
  • SNCCL patients with all of the following factors at presentation of disease:

    • Lactate dehydrogenase (LDH) > 500 IU/L
    • Unresectable bulky mass > 10 cm
    • Stage IV disease with bone marrow involvement
  • MCL Patients with stage IV disease or in International Prognostic Index (IPI) high- or high-intermediate-risk group at the time of diagnosis
  • Considered at diagnosis to be high- (3 risk factors) or high-intermediate-risk (2 risk factors) based on an age-adjusted IPI
  • Poor prognostic factors at diagnosis include stage III or IV disease, lactate dehydrogenase (LDH) level above normal, or ECOG performance status (PS) 2-4
  • Patients with primary mediastinal large cell lymphoma with or without sclerosis who at diagnosis had elevated LDH level with bulky mediastinal mass > 10 cm associated with a pleural effusion on chest radiography or computer tomography, or who have persistent mediastinal mass with positive disease by post-treatment gallium GA 67 scan
  • Must have attained a complete response or partial response to first-line standard conventional chemotherapy
  • ECOG PS 0-1 OR Karnofsky PS 80-100%
  • Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
  • FEV_1 > 65% of predicted measurement or DLCO ≥ 45% of predicted measurement
  • Cardiac ejection fraction > 50% by echocardiogram
  • Bilirubin ≤ 1.5 x normal
  • SGOT or SGPT ≤ 2 x normal

Exclusion Criteria:

  • Evidence of lymphoma or < 10% lymphomatous involvement of bone by bilateral bone marrow aspiration and biopsy
  • Abnormal cytogenetic study of bone marrow aspirate sample NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
  • Positive HIV antibody
  • Prior malignancies except for adequately treated basal cell or squamous cell carcinoma of the skin
  • Hepatitis B surface antigen positivity
  • Prior bone marrow transplantation

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior bone marrow transplantation
  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: NCT00559104

Locations
United States, Arizona
Good Samaritan Regional Medical Center
Phoenix, Arizona, United States, 85006
United States, California
City of Hope National Medical Center--Main Campus
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Study Chair: Auayporn P. Nademanee, MD City of Hope Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00559104     History of Changes
Other Study ID Numbers: 97133  P30CA033572  CHNMC-97133  CDR0000573523 
Study First Received: November 15, 2007
Results First Received: July 17, 2015
Last Updated: July 17, 2015
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV mantle cell lymphoma
stage III mantle cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Carmustine
Etoposide phosphate
Etoposide
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on September 23, 2016