Rituximab in Pretreated Elderly or Unfit B-CLL Patients

B-Cell Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Study of Rituximab in Addition to Glucocorticoid in Pretreated Elderly or Unfit Patients With Chronic B Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01576588
• Other study ID #: LT-CLL-2s
• Status: Completed
• Phase: Phase 2
• Start date: October 2011
• Est. completion date: June 2019

Study information

• Verified date: December 2019
• Source: Vilnius University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2019
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-Cell Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Rituximab
Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1) and Day 1 (cycles 2 to 4).
• Glucocorticoid
Glucocorticoid (either Dexamethasone or Methyl-prednisolone) infusions will be administered on Days 1 to 3 (cycles 1-4(6)) and should precede the Rituximab infusion.

Locations

Country	Name	City	State
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius

Sponsors (1)

Lead Sponsor	Collaborator
Prof. Dr. Med. Laimonas Griskevicius

Country where clinical trial is conducted

Lithuania, 

References & Publications (3)

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner 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. Erratum in: Blood. 2008 Dec 15;112(13):5259. — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Overall response rate (ORR) is defined according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL 2008) guidelines, as the proportion of patients achieving complete response (CR), CR with minimal residual disease (MRD) negativity (complete molecular remission), nodular partial remission (nPR) and partial response (PR).	3 months +/- 2 weeks after the last treatment cycle.
Secondary	Progression Free Survival	Progression free survival (PFS) will be defined as the interval from entry into the study to disease progression or death.	up to 12 months
Secondary	Number of Participants With Adverse Events	Adverse events NCI CTCAE, version 4.0. Hematological toxicity was evaluated according to IWCLL 2008 guidelines.	6 months.
Secondary	Overall Survival	Overall survival (OS) will be defined as the interval from date of randomization until the date of death from any cause, assessed up to 100 months.	from date of randomization until the date of death from any cause, assessed up to 100 months