Rituximab in Pretreated Elderly or Unfit B-CLL Patients

• Sponsor: Prof. Dr. Med. Laimonas Griskevicius (Other)
• Overall Status: Completed
• CT.gov ID: NCT01576588
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arm: 1
• Actual Duration (Months): 92
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Chronic Lymphocytic Leukemia	Drug: Rituximab; Drug: Glucocorticoid	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Rituximab in Addition to Glucocorticoid in Pretreated Elderly or Unfit Patients With Chronic B Lymphocytic Leukemia
• Actual Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-HDMP 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.	Drug: Rituximab; Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1) and Day 1 (cycles 2 to 4).; Other Names: MabThera ; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [3 months +/- 2 weeks after the last treatment cycle.]

   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

1. Progression Free Survival [up to 12 months]

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

2. Number of Participants With Adverse Events [6 months.]

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

3. Overall Survival [from date of randomization until the date of death from any cause, assessed up to 100 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vilnius University Hospital Santaros Klinikos	Vilnius		Lithuania	08661

Sponsors and Collaborators

• Prof. Dr. Med. Laimonas Griskevicius

Investigators

• Principal Investigator: Laimonas Griskevicius, MD, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Prof. Dr. Med. Laimonas Griskevicius, Principal Investigator, Vilnius University
• ClinicalTrials.gov Identifier: NCT01576588
• Other Study ID Numbers: LT-CLL-2s
• First Posted: Apr 12, 2012
• Last Update Posted: Dec 27, 2019
• Last Verified: Dec 1, 2019

• Keywords provided by Prof. Dr. Med. Laimonas Griskevicius, Principal Investigator, Vilnius University: Chronic lymphocytic leukemia, relapsed, elderly or unfit patients, methylprednisolone, rituximab
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Glucocorticoids

Study Results

Participant Flow

Arm/Group Title	R-HDMP
Arm/Group 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. 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.
Period Title: Overall Study
STARTED	25
COMPLETED	23
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	R-HDMP
Arm/Group 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. 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.
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	25 100%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	73
Sex: Female, Male (Count of Participants)
Female	18 72%
Male	7 28%
Region of Enrollment (Count of Participants)
Lithuania	25 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	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).
Time Frame	3 months +/- 2 weeks after the last treatment cycle.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	R-HDMP
Arm/Group 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. 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.
Measure Participants	25
Count of Participants [Participants]	7 28%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	R-HDMP
Arm/Group 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. 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.
Measure Participants	25
Median (Full Range) [months]	11

3. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patient, who experienced any AE - 23.

Arm/Group Title	R-HDMP
Arm/Group 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. 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.
Measure Participants	25
Count of Participants [Participants]	23 92%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	R-HDMP
Arm/Group Description	Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1)...
Measure Participants	25
Median (Full Range) [months]	68

Adverse Events

Arm/Group Title	R-HDMP
Arm/Group 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. 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.
All Cause Mortality
	R-HDMP
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	R-HDMP
	Affected / at Risk (%)	# Events
Total	9/25 (36%)
Blood and lymphatic system disorders
Febrile neutropenia	3/25 (12%)	3
Neutropenia	2/25 (8%)	2
Thrombocytopenia	1/25 (4%)	1
Cardiac disorders
Extrasystolia	1/25 (4%)	1
Gastrointestinal disorders
Diarea	2/25 (8%)	2
Musculoskeletal and connective tissue disorders
Left femur cervical stress fracture	1/25 (4%)	1
Renal and urinary disorders
Renal insufficiency	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Upper pulmonary infection	1/25 (4%)	1
Social circumstances
Orfarin overdosage	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	R-HDMP
	Affected / at Risk (%)	# Events
Total	23/25 (92%)
Blood and lymphatic system disorders
Anemia	2/25 (8%)	3
Leg edema	2/25 (8%)	2
Cardiac disorders
Hypertention	4/25 (16%)	13
Chest discomfort/pain	2/25 (8%)	2
Endocrine disorders
Hyperglycemia	2/25 (8%)	3
Infections and infestations
Fever	3/25 (12%)	5
Metabolism and nutrition disorders
Hypokalemia	15/25 (60%)	26
hypomagnesemia	2/25 (8%)	3
Nervous system disorders
Headache	2/25 (8%)	2
Insomnia	3/25 (12%)	3
Respiratory, thoracic and mediastinal disorders
Cough	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.