Clinical trial NCT00309881: Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia (CLL) That Did Not Respond to Fludarabine, CLL With Autoimmune Haemolytic Anemia (AIHA) or Richter's Transformation (RT)
Official title: CHOP Plus Rituximab (CHOP-R) in Fludarabine Refractory Chronic Lymphocytic Leukemia (CLL) or CLL With Autoimmune Haemolytic Anemia (AIHA) or Richter's Transformation (RT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
First posted: 2006-04-03
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving more than one drug (combination chemotherapy) together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with chronic lymphocytic leukemia (CLL) that has not responded to fludarabine (closed to entry as of 10/2006), CLL with autoimmune hemolytic anemia, or Richter transformation.

Detailed description: OBJECTIVES:

Primary

* Determine the efficacy, in terms of the rate and quality of remission, of chemotherapy comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone, and rituximab (CHOP-R) in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL) (closed to accrual as of 10/2006), CLL with autoimmune hemolytic anemia, or Richter transformation.
* Determine the incidence of infection in patients on CHOP-R regimen.

Secondary

* Determine the toxicity of this regimen in these patients
* Determine the progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a prospective, multicenter study. Patients are stratified according to disease (chronic lymphocytic leukemia (CLL) (closed to accrual as of 10/2006) vs CLL with autoimmune hemolytic anemia vs Richter transformation).

Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive rituximab IV on day 1 of the second course and each subsequent course. Treatment repeats every 21 days for up to 6 (for patients with CLL) or 8 (for patients with Richter's transformation) courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Confirmed diagnosis of previously treated chronic lymphocytic leukemia (CLL) meeting the following criteria:

  * Binet stage B (Rai stages I and II) or Binet stage C (Rai stages III and IV) disease
  * Rapid disease progression, symptomatic enlarged lymph nodes, or severe B-cell symptoms
* CLL with autoimmune hemolytic anemia allowed
* Richter transformation allowed

PATIENT CHARACTERISTICS:

* Life expectancy \> 3 months
* ECOG performance status 0-3
* No severe organ dysfunction
* No other prior or concurrent neoplasms

PRIOR CONCURRENT THERAPY:

* No more than 4 prior chemotherapy regimens

Primary outcomes:
measure: Rate of remission
measure: Quality of remission
Secondary outcomes:
measure: Toxicity
measure: Progression-free survival
measure: Overall survival
Other outcomes:
Locations:
city: Bad Hersfeld
country: Germany
facility: Kreiskrankenhaus
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Giessen
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
city: Hagen
country: Germany
facility: St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Hamburg
country: Germany
facility: Praxis fur Innere Medizin - Hamburg
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Herne
country: Germany
facility: Marienhospital at Ruhr University Bochum
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Weiden
country: Germany
facility: Haematologische Praxis
city: Wuerzburg
country: Germany
facility: Medizinische Poliklinik, Universitaet Wuerzburg
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Michael Hallek, MD
role: STUDY_CHAIR
References:
citation: Langerbeins P, Busch R, Anheier N, Durig J, Bergmann M, Goebeler ME, Hurtz HJ, Stauch MB, Stilgenbauer S, Dohner H, Fink AM, Cramer P, Fischer K, Wendtner CM, Hallek M, Eichhorst B. Poor efficacy and tolerability of R-CHOP in relapsed/refractory chronic lymphocytic leukemia and Richter transformation. Am J Hematol. 2014 Dec;89(12):E239-43. doi: 10.1002/ajh.23841. Epub 2014 Sep 26.