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2-Weekly CHOP Chemotherapy With Dose-Dense Rituximab for the Treatment of Patients Aged 61 to 80 Years With Aggressive CD-20 Positive B-Cell Lymphomas: A Phase-II/Pharmacokinetic Study (CHOP-R-ESC)


Phase 2
61 Years
80 Years
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

2-Weekly CHOP Chemotherapy With Dose-Dense Rituximab for the Treatment of Patients Aged 61 to 80 Years With Aggressive CD-20 Positive B-Cell Lymphomas: A Phase-II/Pharmacokinetic Study (CHOP-R-ESC)


OBJECTIVES:

Primary

- Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a
CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine,
and prednisone in elderly patients with previously untreated aggressive B-cell
lymphoma.

- To determine whether increased single-doses of rituximab for males can compensate their
lower serum levels.

- Evaluate the safety and toxicity profile of this regimen in male patients.

Secondary

- Determine the rate of complete responses, primary progressions under therapy,
event-free survival, progression-free survival, and overall survival in patients
treated with this regimen.

- Determine the rate of primary progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. All patients undergo the following treatment.

- Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral
prednisone on days -6 to 0.

- Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising
cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV
on day 1 and oral prednisone once daily on days 1-5. Patients also receive
pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP
chemotherapy repeats every 14 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients who show no response after course 4 of
CHOP chemotherapy proceed to salvage chemotherapy off study.

Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky
disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission
(CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4
weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy
proceed to salvage chemotherapy off study.

Patients are then stratified according to center, International Prognostic Index (1-2 vs
3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years
old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.

- Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500
mg/m^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also
receive pegfilgrastim subcutaneously on day 4 of each course.

- Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375
mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28,
and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.

Some patients undergo blood sample collection periodically during and after treatment for
pharmacokinetic studies.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then once a year therafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histological diagnosis of aggressive B-cell lymphoma

- Previously untreated disease

- Stage I-IV disease

- CD20-positive disease

- Any International Prognostic Index (IPI) score

- No secondary lymphoma after prior chemotherapy or radiotherapy

- No primary CNS lymphoma

- No primary gastrointestinal (MALT) lymphoma

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- AST and ALT ≤ 3 times normal unless related to lymphoma

- Bilirubin ≤ 2 mg/dL unless related to lymphoma

- Creatinine ≤ 2 times normal unless related to lymphoma

- Fertile patients must use effective contraception

- No known allergic reactions against foreign proteins

- No active infections requiring systemically administered antibiotics or antiviral
medications

- No noncompensated heart failure

- No dilatative cardiomyopathy

- No coronary heart disease with ST-segment depression in ECG

- No myocardial infarction during the past 6 months

- No chronic lung disease with hypoxemia

- No severe noncompensated hypertension

- No severe noncompensated diabetes mellitus

- No clinical signs of cerebral dysfunction

- No severe psychiatric disease

- No known HIV infection

- No active chronic hepatitis B or C infection

- No other concurrent diseases that exclude the administration of therapy as outlined
by the study protocol

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 12 weeks since prior clinical trial participation

- No prior participation in this study

- No prior therapy, including murine antibody, for this cancer

- No prior organ transplantation

- No concurrent response-adapted radiotherapy ("iceberg radiotherapy")

- No other concurrent anticancer chemotherapy or other study medication

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pharmacokinetics (in first 20 patients of each cohort with a distinct variation of the rituximab schedule) assessed on days -4, -1, 10, 29, 57, 99, 155, 239, 267, 295, 407, and 491 of treatment

Safety Issue:

No

Principal Investigator

Michael G.M. Pfreundschuh, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Universitaetsklinikum des Saarlandes

Authority:

Unspecified

Study ID:

CDR0000454505

NCT ID:

NCT00290667

Start Date:

February 2004

Completion Date:

Related Keywords:

  • Lymphoma
  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • stage I adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • contiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • stage I adult immunoblastic large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • contiguous stage II adult Burkitt lymphoma
  • noncontiguous stage II adult Burkitt lymphoma
  • stage I adult Burkitt lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • contiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • stage I adult diffuse mixed cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • contiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • stage I adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • stage I grade 1 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage I grade 3 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic

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