Trial Outcomes & Findings for Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline (NCT NCT00794820)

Last Updated: 2018-05-08

Results Overview

CR Rate is defined as number of all treated participants with CR as defined by 2008 IWCLL update of NCI-WG response criteria: Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; Complete remission with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts; Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts; Progressive disease (PD): ≥ 50% rise in lymphocyte count to \> 5 x109/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL; Stable disease, defined as not meeting criteria for CR, CRi, PR or PD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

6 months

Results posted on

2018-05-08

Participant Flow

Recruitment Period: All recruitment done at The University of Texas MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	FCR-Multiple Dose Rituximab Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Overall Study STARTED	66
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	FCR-Multiple Dose Rituximab Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Overall Study Adverse Event	11
Overall Study Secondary Malignancies	2
Overall Study Resistant Disease	2
Overall Study Ineligible/Screen Failure	1

Baseline Characteristics

Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FCR-Multiple Dose Rituximab n=66 Participants Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants
Region of Enrollment United States	66 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response. One of the 65 participants was not assessed for response to therapy therefore is not included in analysis. The participant went off study after two months of treatment and was not evaluable for response.

Outcome measures

Outcome measures
Measure	FCR-Multiple Dose Rituximab n=64 Participants Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Complete Remission (CR) Rate of FCR3 in Treatment-naïve Participants With Chronic Lymphocytic Leukemia (CLL) at 6 Months	75 Percentage of Participants

SECONDARY outcome

Timeframe: 6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014.

TTP was defined as time from initiation of treatment to primary refractory disease or CLL progression. TTP was censored for therapy-related myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML) and death in remission. TTP calculated using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	FCR-Multiple Dose Rituximab n=64 Participants Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Remission Duration/Time to Progression (TTP)	81 Months Interval 1.0 to 130.0

SECONDARY outcome

Timeframe: 6 months to disease progression, period covered up to 12 years following treatment; Data cutoff for analysis was October 2014.

Population: Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response. One of the 65 participants is not included in analysis, the participant went off study after two months of treatment.

OS was defined as the time from the initiation of treatment to last follow-up date or death. OS were calculated using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	FCR-Multiple Dose Rituximab n=64 Participants Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Overall Survival (OS) Rate	58 Percentage of Participants

Adverse Events

FCR-Multiple Dose Rituximab

Serious events: 30 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	FCR-Multiple Dose Rituximab n=65 participants at risk Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Infections and infestations Infection	36.9% 24/65 • Number of events 31 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Gastrointestinal disorders Vomiting	1.5% 1/65 • Number of events 1 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Chills	1.5% 1/65 • Number of events 1 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Infections and infestations Pneumonia	3.1% 2/65 • Number of events 2 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Pain	3.1% 2/65 • Number of events 2 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Infections and infestations Bacteria Infection	1.5% 1/65 • Number of events 1 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Vascular disorders Thromboembolic event	1.5% 1/65 • Number of events 1 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.

Other adverse events

Other adverse events
Measure	FCR-Multiple Dose Rituximab n=65 participants at risk Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3
Gastrointestinal disorders Nausea	70.8% 46/65 • Number of events 97 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Gastrointestinal disorders Vomiting	9.2% 6/65 • Number of events 7 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Fatigue	64.6% 42/65 • Number of events 68 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Gastrointestinal disorders Diarrhea	12.3% 8/65 • Number of events 11 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Skin and subcutaneous tissue disorders Rash	10.8% 7/65 • Number of events 8 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Edema	10.8% 7/65 • Number of events 9 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Fever	63.1% 41/65 • Number of events 66 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Chills	32.3% 21/65 • Number of events 25 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
General disorders Pain	27.7% 18/65 • Number of events 25 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Infections and infestations Other Infection	6.2% 4/65 • Number of events 4 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Vascular disorders Thromboembolic event	9.2% 6/65 • Number of events 6 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Blood and lymphatic system disorders Anemia	10.8% 7/65 • Number of events 8 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.
Blood and lymphatic system disorders Neutropenia	27.7% 18/65 • Number of events 20 • Adverse events collected through 6 courses; courses repeated every 4-6 weeks, up to 36 weeks. Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.

Additional Information

Susan O'Brien, MD/ Leukemia

University of Texas (UT) MD Anderson Cancer Center

Phone: 1-877-632-6789

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place