Clinical trial NCT01576588: Rituximab in Pretreated Elderly or Unfit B-CLL Patients
Official title: Study of Rituximab in Addition to Glucocorticoid in Pretreated Elderly or Unfit Patients With Chronic B Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-Cell Chronic Lymphocytic Leukemia
Keywords: Chronic lymphocytic leukemia, relapsed, elderly or unfit patients, methylprednisolone, rituximab
Lead sponsor: Vilnius University
Sponsor class: OTHER
First posted: 2012-04-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will test the efficacy rituximab in addition to glucocorticoids for the treatment of B-CLL in elderly or unfit patients.

Detailed description: Patient Population: Pretreated patients with symptomatic B-CLL 18-64 years of age with poor performance status or \>/=65 years of age with any performance status.

Treatment: Up-to 4 cycles of glucocorticoid (Methylprednisolone or Dexamethasone) and Rituximab every 21 day.

Study Duration: The study period for each subject is expected to be 21 months. Subjects will receive up-to 4 cycles of IV infusion of Rituximab and Glucocorticoid. Maximum duration of treatment is expected to be 6 months. Subjects will complete scheduled visits not later than Study Month 21, thereafter they will enter into the long-term follow-up period. Subjects will be followed every 3 months for disease progression, initiation of subsequent leukemia treatment or survival.

Eligibility criteria: Inclusion Criteria:

* The diagnosis of CD20 positive chronic B lymphocytic leukemia (BCLL) confirmed by biopsy or flow-cytometry.
* Previously treated patients with stage Rai I-IV and progressive disease (according to IWCLL 2008 guidelines).

Active B-CLL is defined by at least one of the following:

At least one of the disease related symptoms:

* Constitutional symptoms:
* Weight loss \>10% within the previous 6 months;
* Fatigue (e.g., WHO performance status \>/=2);
* Fever \>/=38C \>/=2 weeks without evidence of infection;
* Night sweats for more than 1 month without evidence of infection.
* Evidence of progressive marrow failure as manifested by development of, or worsening of, anemia and/or thrombocytopenia
* Autoimmune hemolysis and/or thrombocytopenia poorly responsive to corticosteroid therapy.
* Massive (i.e., \>/=6 cm bellow left costal margin) or progressive or symptomatic splenomegaly.
* Massive lymphadenopathy or conglomerates (i.e., \>/=10 cm in largest diameter) or progressive or symptomatic lymphadenopathy.
* Progressive lymphocytosis with an increase \>50% over a 2-month period or an anticipated doubling time of less than 6 months. In patients with initial blood lymphocyte counts of less than 30x10\^9/L LDT should not be used as a single parameter to define treatment indication. Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for protocol therapy.
* Either of the following:
* 18 years of age or older with impaired performance status (CIRS \> 6) and /or
* 65 years of age or older with any performance status.
* Signed informed consent form.

Exclusion Criteria:

* Intolerance to exogenous protein or known severe reaction to the administration of Rituximab.
* Active infection.
* Cancer radiotherapy, biological therapy or chemotherapy within 3 weeks prior to Study Day 1.
* TBC or fungal infection within the past 6 months even if adequately controlled by treatment.
* Severe organ deficiency preventing the participation in the study.
* Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.
* Active peptic ulcer.
* Inadequately controlled diabetes mellitus.
* Suspected or confirmed B-CLL CNS disease.
* Known to be HIV positive.
* Difficult to control, uncooperative patients.
* Allergic disorders in need of chronic glucocorticoid therapy.
* Other oncological diseases requiring active treatment (except hormonal therapy).
* Pregnancy and breastfeeding.
* Patients of reproductive potential who are not using effective methods of contraception.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 3 months +/- 2 weeks after the last treatment cycle.
Secondary outcomes:
measure: Progression Free Survival
timeFrame: up to 12 months
measure: Number of Participants With Adverse Events
timeFrame: 6 months.
measure: Overall Survival
timeFrame: from date of randomization until the date of death from any cause, assessed up to 100 months
Other outcomes:
Locations:
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
Study officials:
affiliation: Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos
name: Laimonas Griskevicius, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pileckyte R, Jurgutis M, Valceckiene V, Stoskus M, Gineikiene E, Sejoniene J, Degulys A, Zvirblis T, Griskevicius L. Dose-dense high-dose methylprednisolone and rituximab in the treatment of relapsed or refractory high-risk chronic lymphocytic leukemia. Leuk Lymphoma. 2011 Jun;52(6):1055-65. doi: 10.3109/10428194.2011.562572.
citation: Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23.
citation: Pileckyte R, Valceckiene V, Stoskus M, Matuzeviciene R, Sejoniene J, Zvirblis T, Griskevicius L. Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia. Medicina (Kaunas). 2019 Oct 29;55(11):719. doi: 10.3390/medicina55110719.