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Comparison of Two Salvage Chemotherapy Regimens Before Autologous Stem Cell Transplantation With or Without Maintenance Rituximab in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2009
First Received: March 8, 2004   Last Updated: April 29, 2009   History of Changes
Sponsored by: National Cancer Institute of Canada
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00078949
  Purpose

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: cisplatin
Drug: cytarabine
Drug: dexamethasone
Drug: gemcitabine hydrochloride
Procedure: observation
Phase III

MedlinePlus related topics: Cancer Lymphoma
Drug Information available for: Dexamethasone Cytarabine hydrochloride Cisplatin Dexamethasone acetate Doxiproct plus Gemcitabine Gemcitabine hydrochloride Rituximab Cytarabine Dexamethasone Sodium Phosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase III Study Of Gemcitabine, Dexamethasone, And Cisplatin (GDP) Compared To Dexamethasone, Cytarabine, And Cisplatin (DHAP) As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggresive Histology Non-Hodgkin's Lymphoma Prior To Autologous Stem Cell Transplant And Followed By Maintenance Rituximab Versus Observation

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

Primary Outcome Measures:
  • Response rate of patients on treatment arm I after 2 courses of chemotherapy [ Designated as safety issue: No ]
  • Transplantation rate of patients on treatment arm I after 2 courses of chemotherapy [ Designated as safety issue: No ]
  • Event-free survival of patients on treatment arm II at 2 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event-free and overall survival of patients on treatment arm I at 2 years [ Designated as safety issue: No ]
  • Mobilization rate of patients on treatment arm I assessed by CD34 count after 2 courses of therapy and stem cell harvesting [ Designated as safety issue: No ]
  • Toxicity assessed by NCI CTC v2.0 after last course of chemotherapy or stem cell transplantation in patients on treatment arm I [ Designated as safety issue: Yes ]
  • Quality of life of patients on treatment arm I assessed by FACT-G after the last course of chemotherapy or stem cell transplantation [ Designated as safety issue: No ]
  • Economic analysis of treatment arm I after the last course of chemotherapy or stem cell transplantation [ Designated as safety issue: No ]
  • Overall survival of patients on treatment arm II at 2 years [ Designated as safety issue: No ]
  • Toxicity assessed by NCI CTC v2.0 for 2 years in patients on treatment arm II [ Designated as safety issue: Yes ]

Estimated Enrollment: 630
Study Start Date: August 2003
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Salvage arm I: Experimental
Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8.
Drug: cisplatin
Given IV
Drug: dexamethasone
Given IV
Drug: gemcitabine hydrochloride
Given IV
Salvage arm II: Experimental
Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2.
Drug: cisplatin
Given IV
Drug: cytarabine
Given IV
Drug: dexamethasone
Given IV
Maintenance arm I: Experimental
Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
Procedure: observation
No treatment given in maintenance phase
Maintenance arm II: No Intervention
Patients undergo observation only.
Biological: rituximab
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:

    • Diffuse large cell lymphoma (includes primary mediastinal B-cell lymphoma and T-cell-rich B-cell lymphoma)
    • Prior indolent lymphoma (e.g., follicular center cell lymphoma; marginal zone lymphoma, including extranodal mucosa-associated lymphoid tissue [MALT] lymphoma; and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse

      • Must be histologically confirmed
      • No transformed lymphoma at diagnosis with subsequent indolent histology without transformation at relapse
    • Peripheral T-cell lymphoma
    • Anaplastic large cell lymphoma
    • Small noncleaved Burkitt-like lymphoma
  • T-cell or B-cell lineage confirmed by immunohistochemistry
  • Clinically or radiologically documented disease meeting either of the following criteria:

    • Measurable disease, defined as at least 1 bidimensionally measurable site of disease using clinical exam, CT scan, or MRI

      • Lymph nodes must be > 1.5 cm by physical exam or CT scan
      • Other non-nodal lesions must be ≥ 1.0 cm by physical exam, CT scan, or MRI
      • Bone lesions are not considered measurable
    • Evaluable disease, defined as only nonmeasurable disease, including any of the following:

      • Marrow infiltration
      • Cytology-confirmed ascites or effusions
      • Bony involvement
      • Enlarged liver or spleen
      • Unidimensionally measurable intrathoracic or abdominal masses
  • Previously treated with 1, and only 1, chemotherapy regimen including an anthracycline and excluding cisplatin, cytarabine, and gemcitabine
  • No uncontrolled CNS involvement by lymphoma

    • No CNS disease at time of relapse
    • CNS disease diagnosed at initial presentation allowed provided a complete response for CNS disease was achieved and maintained

PATIENT CHARACTERISTICS:

Age

  • 16 to 65

Performance status

  • ECOG 0-3

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Absolute granulocyte count ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)
  • Hepatitis B status known (for patients with a history of hepatitis B or who are at high risk of hepatitis B infection)

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No significant cardiac dysfunction or cardiovascular disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to complete quality of life questionnaires
  • HIV negative
  • No active, uncontrolled bacterial, fungal, or viral infection
  • No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • No other concurrent serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Chemotherapy
  • Prior rituximab allowed

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior IV chemotherapy
  • No prior high-dose chemotherapy with stem cell transplantation

Endocrine therapy

  • No concurrent corticosteroids except for physiologic replacement

Radiotherapy

  • At least 4 weeks since prior radiotherapy and recovered

    • Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
  • No prior radiotherapy to more than 25% of functioning bone marrow
  • Involved-field radiotherapy may be given to areas of bulky disease at relapse (≥ 5 cm) after stem cell transplantation, according to the center's policy

Surgery

  • At least 2 weeks since prior major surgery

Other

  • No other concurrent anticancer therapy
  • No other concurrent experimental agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078949

  Show 32 Study Locations
Sponsors and Collaborators
National Cancer Institute of Canada
Investigators
Study Chair: Michael R. Crump, MD, FRCPC Princess Margaret Hospital, Canada
Investigator: Massimo Federico, MD Azienda Ospedaliera - Universitaria di Modena
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000353203, CAN-NCIC-LY12
Study First Received: March 8, 2004
Last Updated: April 29, 2009
ClinicalTrials.gov Identifier: NCT00078949     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
anaplastic large cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
angioimmunoblastic T-cell lymphoma

Study placed in the following topic categories:
Anti-Inflammatory Agents
Dexamethasone
Antimetabolites
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Lymphoma, Small Cleaved-cell, Diffuse
Cisplatin
Lymphoma, T-Cell
Lymphoma, Large-Cell, Anaplastic
Aggression
Lymphoma, Large-cell
Gemcitabine
Lymphoma
Cytarabine
Dexamethasone acetate
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Rituximab
Immunoblastic Lymphadenopathy
Glucocorticoids
Immunosuppressive Agents
Antiviral Agents
Recurrence
Lymphatic Diseases
Burkitt's Lymphoma
Radiation-Sensitizing Agents

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Dexamethasone
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cisplatin
Therapeutic Uses
Gemcitabine
Lymphoma
Cytarabine
Dexamethasone acetate
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Gastrointestinal Agents
Enzyme Inhibitors
Glucocorticoids
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases

ClinicalTrials.gov processed this record on May 07, 2009