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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
carmustine
cyclophosphamide
etoposide
autologous hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
G-CSF
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

16 Years - 59 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Good Samaritan Regional Medical Center
  • City of Hope National Medical Center--Main Campus

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Irradiation in conditioning

Carmustine in conditioning

Arm Description

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

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

Outcomes

Primary Outcome Measures

Progression
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
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
Patient may be assessed for toxicities any time after transplant, up to death, last contact date, or end-of-study date.

Full Information

First Posted
November 15, 2007
Last Updated
July 17, 2015
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00559104
Brief Title
Combination Chemotherapy With or Without Total-Body Irradiation Followed By Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
October 1998 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Irradiation in conditioning
Arm Type
Active Comparator
Arm Description
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
Arm Title
Carmustine in conditioning
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
carmustine
Other Intervention Name(s)
BCNU
Intervention Description
Unique to the Carmustine in Conditioning arm
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan, CTX
Intervention Description
Used in Both Arms
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
VP-16
Intervention Description
Used in Both Arms
Intervention Type
Procedure
Intervention Name(s)
autologous hematopoietic stem cell transplantation
Intervention Description
Both arms are given autologous stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
Both arms are given peripheral blood stem cell transplantation (Peripheral blood stem cells are the material, autologous transplant is the modality).
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Intervention Description
Unique to the Radiation in Conditioning Arm
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Granulocyte-colony stimulating factor
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression
Description
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.
Time Frame
Assessed at date of progression post-transplant
Title
Mortality
Description
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.
Time Frame
Assessed at date of death post-transplant
Secondary Outcome Measure Information:
Title
Short-term and Long-term Treatment-related Toxicities
Description
Patient may be assessed for toxicities any time after transplant, up to death, last contact date, or end-of-study date.
Time Frame
Any time after transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Auayporn P. Nademanee, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Good Samaritan Regional Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
City of Hope National Medical Center--Main Campus
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11707813
Citation
Nademanee A, Molina A, Dagis A, Snyder DS, O'Donnell MR, Parker P, Stein A, Smith E, Planas I, Kashyap A, Spielberger R, Fung H, Krishnan A, Bhatia R, Wong KK, Somlo G, Margolin K, Chow W, Sniecinski I, Vora N, Slovak M, Niland JC, Forman SJ. Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma. Clin Lymphoma. 2000 Jun;1(1):46-54. doi: 10.3816/clm.2000.n.004.
Results Reference
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Combination Chemotherapy With or Without Total-Body Irradiation Followed By Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

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