Trial Outcomes & Findings for Rituximab, Alemtuzumab, and GM-CSF As First-Line Therapy in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia (NCT NCT00562328)

Last Updated: 2020-04-08

Results Overview

Response, as defined by the National Cancer Institute Working Group (NCIWG), requires the following for a period of at least 2 months: * CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy * PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, \>100,000/μL platelets, \>11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

6 months

Results posted on

2020-04-08

Participant Flow

Thirty-three (33) participants were recruited at Mayo Clinic (Rochester and Arizona) between January 2008 and February 2010.

All patients were deemed eligible.

Participant milestones

Participant milestones
Measure	Alemtuzumab + Rituximab + GM-CSF Alemtuzumab + Rituximab + GM-CSF
Overall Study STARTED	33
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rituximab, Alemtuzumab, and GM-CSF As First-Line Therapy in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 Participants Alemtuzumab + Rituximab + GM-CSF
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants
Region of Enrollment United States	33 participants n=5 Participants
Rai Stage Stage 0	2 participants n=5 Participants
Rai Stage Stage 1	27 participants n=5 Participants
Rai Stage Stage 2	4 participants n=5 Participants
CD38 Expression Status Positive (>=30%)	15 participants n=5 Participants
CD38 Expression Status Negative (<30%)	18 participants n=5 Participants
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status Mutated	3 participants n=5 Participants
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status Unmutated	30 participants n=5 Participants
ZAP-70 Expression Positive (>=20%)	25 participants n=5 Participants
ZAP-70 Expression Negative (<20%)	7 participants n=5 Participants
ZAP-70 Expression Unknown	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 Participants Patients received Alemtuzumab + Rituximab + GM-CSF.
Number of Confirmed Responses (Complete or Partial Response Noted as the Objective Status for a Duration of at Least 2 Months) at 6 Months	31 Participants

SECONDARY outcome

Timeframe: Time from registration to progression (up to 5 years)

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to the standard NCI-WG96 criteria. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 Participants Patients received Alemtuzumab + Rituximab + GM-CSF.
Progression Free Survival	13.0 months Interval 9.4 to The 95% confidence interval upper limit was not yet reached (below the level of detection).

SECONDARY outcome

Timeframe: time from start of response to progression (up to 5 years)

Population: Only patients who responded to treatment are included in this analysis.

Duration of response (DOR) is defined as the time from documentation of response (CR or PR) to disease progression. The median DOR with 95% CI was estimated using the Kaplan Meier method.Response, as defined by the National Cancer Institute Working Group (NCIWG), requires the following for a period of at least 2 months: * CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy * PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, \>100,000/μL platelets, \>11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions

Outcome measures

Outcome measures
Measure	Alemtuzumab + Rituximab + GM-CSF n=31 Participants Patients received Alemtuzumab + Rituximab + GM-CSF.
Duration of Response	14.9 months Interval 8.8 to The 95% confidence interval upper limit was not yet reached (below the level of detection).

SECONDARY outcome

Timeframe: time from end of protocol treatment to subsequent treatment (up to 5 years)

Time to next treatment was defined as the time from end of active (protocol) treatment to the start of subsequent treatment. The median and 95% CI was estimated using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 Participants Patients received Alemtuzumab + Rituximab + GM-CSF.
Time to Next Treatment	33.5 months Interval 25.5 to The 95% confidence interval upper limit was not yet reached (below the level of detection).

SECONDARY outcome

Timeframe: Time from registration to death (up to 5 years)

Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 Participants Patients received Alemtuzumab + Rituximab + GM-CSF.
Overall Survival	NA months Median and 95% confidence interval for overall survival has not been reached (below the level of detection).

Adverse Events

Alemtuzumab + Rituximab + GM-CSF

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 participants at risk Alemtuzumab + Rituximab + GM-CSF
Infections and infestations Pneumonia	3.0% 1/33 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	3.0% 1/33 • Number of events 1

Other adverse events

Other adverse events
Measure	Alemtuzumab + Rituximab + GM-CSF n=33 participants at risk Alemtuzumab + Rituximab + GM-CSF
Blood and lymphatic system disorders Anemia	6.1% 2/33 • Number of events 2
Blood and lymphatic system disorders Febrile neutropenia	3.0% 1/33 • Number of events 1
Eye disorders Vitreous hemorrhage	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Constipation	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Mucositis oral	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Nausea	3.0% 1/33 • Number of events 1
General disorders Chills	9.1% 3/33 • Number of events 4
General disorders Fatigue	12.1% 4/33 • Number of events 5
General disorders Fever	72.7% 24/33 • Number of events 43
General disorders Injection site reaction	3.0% 1/33 • Number of events 1
Immune system disorders Hypersensitivity	3.0% 1/33 • Number of events 1
Infections and infestations Blood Infection	9.1% 3/33 • Number of events 5
Infections and infestations Bronchial infection	3.0% 1/33 • Number of events 1
Infections and infestations Infection without neutropenia	6.1% 2/33 • Number of events 5
Infections and infestations Lip infection	3.0% 1/33 • Number of events 1
Infections and infestations Opportunisitic infection	9.1% 3/33 • Number of events 6
Infections and infestations Pharyngitis	6.1% 2/33 • Number of events 2
Infections and infestations Pneumonia	3.0% 1/33 • Number of events 1
Infections and infestations Respiratory tract infection	18.2% 6/33 • Number of events 9
Investigations Bilirubin	3.0% 1/33 • Number of events 3
Investigations Leukopenia	48.5% 16/33 • Number of events 39
Investigations Lymphocyte count decreased	3.0% 1/33 • Number of events 2
Investigations Neutrophil count decreased	21.2% 7/33 • Number of events 17
Investigations Platelet count decreased	3.0% 1/33 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	3.0% 1/33 • Number of events 1
Musculoskeletal and connective tissue disorders Pain in extremity	3.0% 1/33 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	3.0% 1/33 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.0% 1/33 • Number of events 1
Skin and subcutaneous tissue disorders Dermatology	3.0% 1/33 • Number of events 1
Skin and subcutaneous tissue disorders Rash	75.8% 25/33 • Number of events 59
Skin and subcutaneous tissue disorders Sweating	6.1% 2/33 • Number of events 4

Additional Information

Timothy G. Call, M.D.

Mayo Clinic

Phone: 507-266-4671

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place