Trial Outcomes & Findings for Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (NCT NCT00290810)

Last Updated: 2014-05-09

Results Overview

The NCI Working Group criteria will be used to assess response to therapy. A confirmed response is defined as a response documented on 2 consecutive evaluations at least 4 weeks apart. Complete Response: * No lymphadenopathy * No hepatomegaly or splenomegaly * Absense of constitutional symptoms * Polymorphonuclear leukocytes ≥ 1500/ul * Platelets \> 100,000/ul * Hemoglobin \> 11.0 gm/dl * Peripheral blood lymphocytes ≤ 4000/uL. * Confirmation by Marrow Aspirate and biopsy. Complete Clinical Response: -CR without bone marrow biopsy confirmation. Nodular Partial Response: -CR with the presence of residual clonal nodules. Partial Response requires: * ≥ 50% decrease in peripheral blood lymphocyte count * ≥ 50% reduction in lymphadenopathy * ≥ 50% reduction in size of liver and/or spleen * 1 or more of the following: * Polymorphonuclear leukocytes ≥ 1500/ul * Platelets \>100,000/ul * Hemoglobin \>11.0 gm/dl

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2014-05-09

Participant Flow

Thirteen patients were accrued to the bevacizumab trial between December 2005 and March 2009.

One patient never received protocol treatment due to a high protein:creatinine ratio and high 24-hour urine protein excretion. Accordingly, 12 eligible patients were included in the outcome analysis.

Participant milestones

Participant milestones
Measure	Treatment (Monoclonal Antibody Therapy) Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Monoclonal Antibody Therapy) n=12 Participants Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	73 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: All 12 patients are used in this analysis

Outcome measures

Outcome measures
Measure	Treatment (Monoclonal Antibody Therapy) n=12 Participants Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR). Complete Response (CR)	0 participants
Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR). Complete Clinical Response (CCR)	0 participants
Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR). Nodular Partial Response (nPR)	0 participants
Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR). Partial Response (PR)	0 participants

SECONDARY outcome

Timeframe: From the date of registration to the to the date of last treatment evaluation, median number of days on treatment was 56 days.

Population: All 12 participants treated will be used to analyze this endpoint.

As per NCI Common Toxicity Criteria for Adverse Effects (CTCAE) Version 3.0, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The number of participants experiencing grade 3 or higher toxicity will be reported here.

Outcome measures

Outcome measures
Measure	Treatment (Monoclonal Antibody Therapy) n=12 Participants Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Toxicity Associated With This Regimen in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). Grade 3 Toxicity	5 participants
Toxicity Associated With This Regimen in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). Grade 4 Toxicity	1 participants

SECONDARY outcome

Timeframe: From the date of registration to the date of the event (i.e., death or the date of last follow-up), up to 5 years.

The Kaplan-Meier method will be used to estimate distributions in the B-CLL population.

Outcome measures

Outcome measures
Measure	Treatment (Monoclonal Antibody Therapy) n=12 Participants Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	39.75 months Interval 5.65 to Too few events occurred to obtain an estimate.

SECONDARY outcome

Timeframe: From the date of registration to the date of the event (i.e., death or disease progression) or the date of last follow-up, up to 5 years

Progression is defined as one of the following: * A ≥50% increase in the sum of the products of at least 2 lymph nodes on 2 consecutive determinations 2 weeks apart (at least one node must be ≥2 cm) or the appearance of new palpable lymph nodes, or * A ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin or the appearance of hepatomegaly or splenomegaly which was not previously present, or * The transformation to a more aggressive histology (e.g. Richter's transformation), or * A ≥ 50% increase in the absolute number of circulating lymphocytes. The Kaplan-Meier method will be used to estimate time to progression.

Outcome measures

Outcome measures
Measure	Treatment (Monoclonal Antibody Therapy) n=12 Participants Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Time to Progression	2.9 months Interval 1.8 to 3.7

Adverse Events

Treatment (Monoclonal Antibody Therapy)

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Monoclonal Antibody Therapy) n=12 participants at risk Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cardiac disorders Atrial fibrillation	8.3% 1/12 • Number of events 2
Eye disorders Eye disorder	8.3% 1/12 • Number of events 1
General disorders Fatigue	16.7% 2/12 • Number of events 2
Infections and infestations Pneumonia	8.3% 1/12 • Number of events 1
Nervous system disorders Headache	8.3% 1/12 • Number of events 1

Other adverse events

Other adverse events
Measure	Treatment (Monoclonal Antibody Therapy) n=12 participants at risk Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Hemoglobin decreased	25.0% 3/12 • Number of events 5
Blood and lymphatic system disorders Lymph node pain	8.3% 1/12 • Number of events 1
Ear and labyrinth disorders External ear inflammation	8.3% 1/12 • Number of events 1
Endocrine disorders Hyperthyroidism	16.7% 2/12 • Number of events 2
Gastrointestinal disorders Dysphagia	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Esophagitis	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Nausea	25.0% 3/12 • Number of events 4
Gastrointestinal disorders Vomiting	16.7% 2/12 • Number of events 2
General disorders Edema limbs	8.3% 1/12 • Number of events 1
General disorders Fatigue	58.3% 7/12 • Number of events 12
General disorders Fever	8.3% 1/12 • Number of events 1
Infections and infestations Sinusitis	8.3% 1/12 • Number of events 1
Infections and infestations Urinary tract infection	8.3% 1/12 • Number of events 1
Investigations Alkaline phosphatase increased	8.3% 1/12 • Number of events 2
Investigations Creatinine increased	33.3% 4/12 • Number of events 5
Investigations Neutrophil count decreased	8.3% 1/12 • Number of events 1
Investigations Platelet count decreased	25.0% 3/12 • Number of events 7
Metabolism and nutrition disorders Anorexia	8.3% 1/12 • Number of events 2
Metabolism and nutrition disorders Blood glucose increased	16.7% 2/12 • Number of events 3
Metabolism and nutrition disorders Serum calcium decreased	8.3% 1/12 • Number of events 2
Metabolism and nutrition disorders Serum potassium decreased	8.3% 1/12 • Number of events 1
Nervous system disorders Dizziness	8.3% 1/12 • Number of events 1
Nervous system disorders Headache	33.3% 4/12 • Number of events 6
Psychiatric disorders Anxiety	8.3% 1/12 • Number of events 1
Psychiatric disorders Depression	8.3% 1/12 • Number of events 1
Renal and urinary disorders Proteinuria	41.7% 5/12 • Number of events 8
Respiratory, thoracic and mediastinal disorders Dyspnea	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders Epistaxis	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pharyngeal examination abnormal	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders Respiratory disorder	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders Voice alteration	8.3% 1/12 • Number of events 5
Skin and subcutaneous tissue disorders Sweating	8.3% 1/12 • Number of events 1
Vascular disorders Hypertension	33.3% 4/12 • Number of events 4

Additional Information

Tait Shanafelt, M.D.

Mayo Clinic

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60