Trial Outcomes & Findings for Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia (NCT NCT00230282)

Results Overview

Response criteria as per the NCI-WG Revised Guidelines for B-CLL Complete remission: No lymphadenopathy by physical exam No hepatomegaly or splenomegaly Absence of constitutional symptoms Polymorphonuclear leukocytes \> 1,500/uL, Platelets \> 100,000/uL, Hemoglobin \> 11.0 g/dL Bone marrow aspirate and biopsy normocellular with \< 30% lymphocytes Absent lymphoid nodules Partial remission: * 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value * 50% reduction in lymphadenopathy and/or ≥ 50% reduction in the size of the liver and/or spleen AND one or more of the following Polymorphonuclear leukocytes \> 1,500/uL or 50% improvement over baseline Platelets \> 100,000/uL or 50% improvement over baseline Hemoglobin \> 11.0 g/dL or 50% improvement over baseline

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

24 weeks

Results posted on

2014-10-06

Participant Flow

Participant milestones

Participant milestones
Measure	Fludarabine and Cyclophosphamide, Followed by Alemtuzumab Fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC on days 1 to 3 for each of six 28-day cycles, when the assessment for Primary Completion occurred. Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive alemtuzumab IV starting at 3 mg/day with the dose adjusted to the maximum tolerated dose (up to 30 mg).
Fludarabine + Cyclophosphamide STARTED	25
Fludarabine + Cyclophosphamide COMPLETED	17
Fludarabine + Cyclophosphamide NOT COMPLETED	8
Maintanence Therapy With Alemtuzumab STARTED	17
Maintanence Therapy With Alemtuzumab COMPLETED	17
Maintanence Therapy With Alemtuzumab NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Fludarabine and Cyclophosphamide, Followed by Alemtuzumab Fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC on days 1 to 3 for each of six 28-day cycles, when the assessment for Primary Completion occurred. Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive alemtuzumab IV starting at 3 mg/day with the dose adjusted to the maximum tolerated dose (up to 30 mg).
Fludarabine + Cyclophosphamide Lost to Follow-up	4
Fludarabine + Cyclophosphamide Withdrawal by Subject	1
Fludarabine + Cyclophosphamide Change in diagnosis	1
Fludarabine + Cyclophosphamide Richters transformation (progression)	2

Baseline Characteristics

Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fludarabine and Cyclophosphamide, Followed by Alemtuzumab n=25 Participants Fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC on days 1 to 3 for each of six 28-day cycles, when the assessment for Primary Completion occurred. Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive alemtuzumab IV starting at 3 mg/day with the dose adjusted to the maximum tolerated dose (up to 30 mg).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Response criteria as per the NCI-WG Revised Guidelines for B-CLL Complete remission: No lymphadenopathy by physical exam No hepatomegaly or splenomegaly Absence of constitutional symptoms Polymorphonuclear leukocytes \> 1,500/uL, Platelets \> 100,000/uL, Hemoglobin \> 11.0 g/dL Bone marrow aspirate and biopsy normocellular with \< 30% lymphocytes Absent lymphoid nodules Partial remission: * 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value * 50% reduction in lymphadenopathy and/or ≥ 50% reduction in the size of the liver and/or spleen AND one or more of the following Polymorphonuclear leukocytes \> 1,500/uL or 50% improvement over baseline Platelets \> 100,000/uL or 50% improvement over baseline Hemoglobin \> 11.0 g/dL or 50% improvement over baseline

Outcome measures

Outcome measures
Measure	Fludarabine and Cyclophosphamide, Followed by Alemtuzumab n=25 Participants Fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC on days 1 to 3 for each of six 28-day cycles, when the assessment for Primary Completion occurred. Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive alemtuzumab IV starting at 3 mg/day with the dose adjusted to the maximum tolerated dose (up to 30 mg).
Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR)	17 participants

SECONDARY outcome

Timeframe: 105 months

Outcome measures

Outcome measures
Measure	Fludarabine and Cyclophosphamide, Followed by Alemtuzumab n=17 Participants Fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC on days 1 to 3 for each of six 28-day cycles, when the assessment for Primary Completion occurred. Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive alemtuzumab IV starting at 3 mg/day with the dose adjusted to the maximum tolerated dose (up to 30 mg).
Duration of Response	38 months Interval 12.0 to 105.0

Adverse Events

Fludarabine, Cytoxan, Then Alemtuzumab

Serious events: 5 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Fludarabine, Cytoxan, Then Alemtuzumab n=25 participants at risk Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed. Alemtuzumab: 3 to 30 mg, IV Fludarabine: \[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl\]methoxyphosphonic acid Cytoxan: (RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
Blood and lymphatic system disorders febrile neutropenia	4.0% 1/25
Blood and lymphatic system disorders anemia	4.0% 1/25
Respiratory, thoracic and mediastinal disorders pneumonitis	4.0% 1/25
Infections and infestations lung infection	4.0% 1/25
Blood and lymphatic system disorders hemolysis	4.0% 1/25

Other adverse events

Other adverse events
Measure	Fludarabine, Cytoxan, Then Alemtuzumab n=25 participants at risk Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed. Alemtuzumab: 3 to 30 mg, IV Fludarabine: \[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl\]methoxyphosphonic acid Cytoxan: (RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
Blood and lymphatic system disorders anemia	4.0% 1/25
Gastrointestinal disorders mucositis	4.0% 1/25

Additional Information

Steven E. Coutre, Associate Professor of Medicine

Stanford University

Phone: 650-723-6661

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place