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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00078949




Registration number
NCT00078949
Ethics application status
Date submitted
8/03/2004
Date registered
9/03/2004
Date last updated
7/04/2020

Titles & IDs
Public title
Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
Scientific title
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 vs Observation
Secondary ID [1] 0 0
CAN-NCIC-LY12
Secondary ID [2] 0 0
LY12
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - rituximab
Treatment: Drugs - cisplatin
Treatment: Drugs - cytarabine
Treatment: Drugs - dexamethasone
Treatment: Drugs - gemcitabine hydrochloride

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.

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.

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.

No Intervention: Maintenance arm II - Patients undergo observation only.


Other interventions: rituximab
Given IV

Treatment: Drugs: cisplatin
Given IV

Treatment: Drugs: cytarabine
Given IV

Treatment: Drugs: dexamethasone
Given IV

Treatment: Drugs: gemcitabine hydrochloride
Given IV

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Response Rate of Patients After 2 Courses of Chemotherapy - The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).
Timepoint [1] 0 0
After 2 cycle of treatment
Primary outcome [2] 0 0
Transplantation Rate of Patients After 2 Courses of Chemotherapy - Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients
Timepoint [2] 0 0
During period 1 (salvage chemotherapy)
Primary outcome [3] 0 0
Event-free Survival of Patients on Maintenance Randomization (Period 2) - Number of patients who develop EFS event during maintenance randomization (period 2)
Timepoint [3] 0 0
during the period 2 (up to10 years)
Secondary outcome [1] 0 0
Toxic Effect - Number of patients affected by adverse events graded according to CTC Version 2.0. See adverse event (others) for details.
Timepoint [1] 0 0
48 months

Eligibility
Key inclusion 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
Minimum age
16 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
Manitoba
Country [8] 0 0
Canada
State/province [8] 0 0
New Brunswick
Country [9] 0 0
Canada
State/province [9] 0 0
Newfoundland and Labrador
Country [10] 0 0
Canada
State/province [10] 0 0
Nova Scotia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Canada
State/province [13] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
NCIC Clinical Trials Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00078949
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael R. Crump, MD, FRCPC
Address 0 0
Princess Margaret Hospital, Canada
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications