Back to results

Rituximab in Pretreated Elderly or Unfit B-CLL Patients

Primary Purpose

B-Cell Chronic Lymphocytic Leukemia

Status

Completed

Phase

Phase 2

Locations

Lithuania

Study Type

Interventional

Intervention

Rituximab

Glucocorticoid

About this trial

This is an interventional treatment trial for B-Cell Chronic Lymphocytic Leukemia focused on measuring Chronic lymphocytic leukemia, relapsed, elderly or unfit patients, methylprednisolone, rituximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Vilnius University Hospital Santaros Klinikos

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R-HDMP

Arm Description

Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1) and Day 1 (cycles 2 to 4). 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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Progression Free Survival

Progression free survival (PFS) will be defined as the interval from entry into the study to disease progression or death.

Number of Participants With Adverse Events

Adverse events NCI CTCAE, version 4.0. Hematological toxicity was evaluated according to IWCLL 2008 guidelines.

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.

Full Information

NCT ID

NCT01576588

First Posted

March 9, 2012

Last Updated

December 17, 2019

Sponsor

Prof. Dr. Med. Laimonas Griskevicius

1. Study Identification

Unique Protocol Identification Number

NCT01576588

Brief Title

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

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

October 2011 (Actual)

Primary Completion Date

January 2016 (Actual)

Study Completion Date

June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Prof. Dr. Med. Laimonas Griskevicius

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B-Cell Chronic Lymphocytic Leukemia

Keywords

Chronic lymphocytic leukemia, relapsed, elderly or unfit patients, methylprednisolone, rituximab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

R-HDMP

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

MabThera

Intervention Description

Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1) and Day 1 (cycles 2 to 4).

Intervention Type

Drug

Intervention Name(s)

Glucocorticoid

Intervention Description

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.

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

Time Frame

3 months +/- 2 weeks after the last treatment cycle.

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

Progression free survival (PFS) will be defined as the interval from entry into the study to disease progression or death.

Time Frame

up to 12 months

Title

Number of Participants With Adverse Events

Description

Adverse events NCI CTCAE, version 4.0. Hematological toxicity was evaluated according to IWCLL 2008 guidelines.

Time Frame

6 months.

Title

Overall Survival

Description

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.

Time Frame

from date of randomization until the date of death from any cause, assessed up to 100 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laimonas Griskevicius, MD

Organizational Affiliation

Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vilnius University Hospital Santaros Klinikos

City

Vilnius

ZIP/Postal Code

08661

Country

Lithuania

12. IPD Sharing Statement

Citations:

PubMed Identifier

21599591

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.

Results Reference

background

PubMed Identifier

18216293

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. Erratum In: Blood. 2008 Dec 15;112(13):5259.

Results Reference

background

PubMed Identifier

31671877

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.

Results Reference

result

Learn more about this trial

Rituximab in Pretreated Elderly or Unfit B-CLL Patients

We'll reach out to this number within 24 hrs