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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00078949
First received: March 8, 2004
Last updated: February 27, 2014
Last verified: February 2014
  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. Rituximab was added to both salvage treatment arms for CD20+ patients in a protocol amendment in 2005.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: cisplatin
Drug: cytarabine
Drug: dexamethasone
Drug: gemcitabine hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study Of Gemcitabine, Dexamethasone, And Cisplatin Compared To Dexamethasone, Cytarabine, And Cisplatin Plus/Minus Rituximab [(R)-GDP vs (R)-DHAP] As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggressive Histology Non-Hodgkin's Lymphoma Prior To Autologous Stem Cell Transplant And Followed By Maintenance Rituximab Versus Observation

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Response rate of patients on treatment arm I after 2 courses of chemotherapy [ Time Frame: 8.5 years ] [ Designated as safety issue: No ]
  • Transplantation rate of patients on treatment arm I after 2 courses of chemotherapy [ Time Frame: 8.5 years ] [ Designated as safety issue: No ]
  • Event-free survival of patients on treatment arm II at 2 years [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event-free and overall survival of patients on treatment arm I at 2 years [ Time Frame: 10 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 [ Time Frame: 10 years ] [ 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 [ Time Frame: 10 years ] [ 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 [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • Economic analysis of treatment arm I after the last course of chemotherapy or stem cell transplantation [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • Overall survival of patients on treatment arm II at 2 years [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • Toxicity assessed by NCI CTC v2.0 for 2 years in patients on treatment arm II [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]

Enrollment: 619
Study Start Date: August 2003
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Salvage arm I
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
Experimental: Salvage arm II
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
Experimental: Maintenance arm I
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.
Biological: rituximab
Given IV
No Intervention: Maintenance arm II
Patients undergo observation only.

  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
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: NCT00078949

  Show 26 Study Locations
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Michael R. Crump, MD, FRCPC Princess Margaret Hospital, Canada
Study Chair: Massimo Federico, MD Azienda Ospedaliera - Universitaria di Modena
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00078949     History of Changes
Obsolete Identifiers: NCT00089817
Other Study ID Numbers: LY12, CAN-NCIC-LY12, CDR0000353203
Study First Received: March 8, 2004
Last Updated: February 27, 2014
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
anaplastic large cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
angioimmunoblastic T-cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Rituximab
Cisplatin
Cytarabine
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics

ClinicalTrials.gov processed this record on August 28, 2014