Trial Outcomes & Findings for FCR Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia (NCT NCT00381004)

Last Updated: 2016-01-14

Results Overview

Complete Remission:Normal exam/No symptoms; Absolute lymphocyte count (ALC)\</=4x10\^9/L, Hb\>11 g/dL, absolute neutrophil count (ANC)\>/=1.5x109/L, \& platelet count\>100x109/L. Bone marrow:\<30% lymphocytes aspirate no biopsy evidence disease; Disappearance palpable lymph nodes/spleen/liver, no new lesions. Partial Remission:ALC reduced 50%,either Hb\>11 g/dL or 50% improvement (imp.) in deviation, or ANC\>/=1.5x109/L or 50% imp., or platelet\>100x109/L or 50% imp. in deviation from normal. Reduced 50% palpable lymph nodes/spleen/liver no new lesions. Nodular Partial Response:ALC\</=4x109/L + Hb\>11 g/dL, ANC\>/=1.5x109/L \& platelet count\>100x109/L; \<30% lymphocytes - bone marrow biopsy aspirate + lymphoid nodules;No palpable lymph nodes/spleen/liver tumors without new lesions. Progressive Disease:50% increase (incr.) ALC\>10x109/L twice; tumor lesion incr. 50% over entry or responder size at time max regression \&/or appearance new malignant disease; Reappearance bone marrow disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Baseline to 6 Months

Results posted on

2016-01-14

Participant Flow

Recruitment Period: September 20, 2006 to June 5, 2008. All recruitment done at The University of Texas MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	FCR + Sargramostim Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Overall Study STARTED	60
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

FCR Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FCR + Sargramostim n=60 Participants Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Age, Continuous	55 years n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 6 Months

Outcome measures

Outcome measures
Measure	FCR + Sargramostim n=60 Participants Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Participant Overall Response Rate (ORR) at 6 Months Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions.	100 Percentage of Participants

PRIMARY outcome

Timeframe: Baseline to 6 Months

Outcome measures

Outcome measures
Measure	FCR + Sargramostim n=60 Participants Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Number of Participants With Overall Response Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions. Complete Response (CR)	45 Participants
Number of Participants With Overall Response Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions. Nodular Partial Response (nPR)	6 Participants
Number of Participants With Overall Response Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions. Partial Response (PD)	9 Participants

SECONDARY outcome

Timeframe: 6 months or until disease progression if earlier

Participants progression free as measured at six months following start of treatment. Criteria for Progressive Disease (PD): Peripheral blood: 50% increase in ALC with a level \> 10 x 109/L on at least 2 occasions 2 weeks apart. Tumor: An increase of a lesion by 50% over the size present at entry on study or for patients who respond, the size at the time of maximum regression and/or the appearance of new areas of malignant disease. Reappearance of bone marrow disease. A deterioration in performance status or increasing symptoms do not constitute disease progression.

Outcome measures

Outcome measures
Measure	FCR + Sargramostim n=60 Participants Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Number of Participants Progression-free	60 participants

Adverse Events

FCR + Sargramostim

Serious events: 12 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	FCR + Sargramostim n=60 participants at risk Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Gastrointestinal disorders DEHYDRATION	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Gastrointestinal disorders DIARRHEA	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
General disorders DEATH	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
General disorders FEVER OF UNKNOWN ORIGIN	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Infections and infestations FEBRILE NEUTROPENIA	3.3% 2/60 • Number of events 2 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Infections and infestations INFECTION	3.3% 2/60 • Number of events 2 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SECONDARY MALIGNANCY DUCTAL CARCINOMA IN SITU RIGHT BREAST	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SECONDARY MALIGNANCY MDS	5.0% 3/60 • Number of events 3 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SECONDARY MALIGNANCY SQUAMOUS CELL CARCINOMA	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Nervous system disorders ENCEPHALOATHY	1.7% 1/60 • Number of events 1 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.
Nervous system disorders SEIZURE	1.7% 1/60 • Number of events 2 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.

Other adverse events

Other adverse events
Measure	FCR + Sargramostim n=60 participants at risk Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m\^2 IV Days 2-4; Course 2-6: 25 mg/m\^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m\^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m\^2 Days 1-3. Rituximab - Course 1: 375 mg/m\^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m\^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m\^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m\^2 SQ Days -1 and 4-10.
Skin and subcutaneous tissue disorders Pain/erythema at injection site	6.7% 4/60 • Number of events 4 • Adverse event collection through total of 6 courses administered, courses are 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and assessments for toxicities after 3 and 6 courses, up to 252 days.

Additional Information

Alessandra Ferrajoli, MD/Professor, Leukemia

The University of Texas (UT) MD Anderson Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place