Trial Outcomes & Findings for Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support (NCT NCT00506857)
NCT ID: NCT00506857
Last Updated: 2012-02-28
Results Overview
Continual reassessment method (four times a day) used to determine an MTD, with a target toxicity probability of 20%, where "toxicity" is defined as grade 3 or 4 conventional toxicity \[National Cancer Institute Common Toxicity Criteria (NCI-CTC)\]. Participant evaluation in a cohort with each modality is 30 days.
COMPLETED
PHASE1/PHASE2
82 participants
1 month
2012-02-28
Participant Flow
Recruitment period: November 2003 to August 2011. All recruitment was done at UT MD Anderson Cancer Center.
Of the 82 participants enrolled, two (2) participants were excluded from the trial before starting treatment.
Participant milestones
| Measure |
Busulfan + Fludarabine
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.
|
|---|---|
|
Overall Study
STARTED
|
80
|
|
Overall Study
COMPLETED
|
80
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support
Baseline characteristics by cohort
| Measure |
Busulfan + Fludarabine
n=80 Participants
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.
|
|---|---|
|
Age Continuous
|
56 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
80 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 1 monthPopulation: Analysis was per protocol.
Continual reassessment method (four times a day) used to determine an MTD, with a target toxicity probability of 20%, where "toxicity" is defined as grade 3 or 4 conventional toxicity \[National Cancer Institute Common Toxicity Criteria (NCI-CTC)\]. Participant evaluation in a cohort with each modality is 30 days.
Outcome measures
| Measure |
Busulfan + Fludarabine
n=80 Participants
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.
|
|---|---|
|
Maximum Tolerated Dose (MTD)
|
11.2 mg/kg
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Analysis was per protocol for 73 patients out of 80 patients due to 3 early deaths and 4 non engraftments.
Tacrolimus and Methotrexate used for acute graft versus host disease (aGVHD) prophylaxis, clinical grading AGVHD criteria (Days 1-100): Grade 1: + to ++ skin rash; no gut involvement; no decrease in clinical performance status; Grade 2: + to +++ skin rash; + gut involvement and/or + liver involvement; mild decrease in performance status; Grade 3: ++ to +++ skin rash; ++ to +++ gut involvement and/or ++ to ++++ liver involvement; marked decrease in performance status; Grade 4: Similar to Grade 3 with ++ to ++++ organ involvement and extreme decrease in performance status.
Outcome measures
| Measure |
Busulfan + Fludarabine
n=73 Participants
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.
|
|---|---|
|
Number of Participants With Graft Versus Host Disease (GVHD)
Grade 2
|
18 Participants
|
|
Number of Participants With Graft Versus Host Disease (GVHD)
Grade 3-4
|
8 Participants
|
Adverse Events
Busulfan + Fludarabine
Serious adverse events
| Measure |
Busulfan + Fludarabine
n=80 participants at risk
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.
|
|---|---|
|
Blood and lymphatic system disorders
Graft failure
|
2.5%
2/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Infections and infestations
Infections
|
15.0%
12/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Respiratory, thoracic and mediastinal disorders
Diffuse alveolar haemorrhage
|
1.2%
1/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
8.8%
7/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
General disorders
Death
|
10.0%
8/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
General disorders
Chronic Graft versus Host Disease
|
11.0%
8/73 • March 2000 to December 2004 (4 years, 8 months)
|
|
Gastrointestinal disorders
Mucositis
|
1.2%
1/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Gastrointestinal disorders
Epistaxis
|
3.8%
3/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
General disorders
Acute Graft versus Host Disease
|
35.6%
26/73 • March 2000 to December 2004 (4 years, 8 months)
|
|
Hepatobiliary disorders
Elevated alanine aminotransferase
|
1.2%
1/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath
|
3.8%
3/80 • March 2000 to December 2004 (4 years, 8 months)
|
Other adverse events
| Measure |
Busulfan + Fludarabine
n=80 participants at risk
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
37.5%
30/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Gastrointestinal disorders
Nausea
|
48.8%
39/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Renal and urinary disorders
Elevated Creatinine
|
40.0%
32/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Renal and urinary disorders
Hemorrhagic cystitis
|
2.5%
2/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Hepatobiliary disorders
Elevated alkaline phosphate
|
3.8%
3/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Nervous system disorders
Altered mental status
|
2.5%
2/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Eye disorders
Occular
|
6.2%
5/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
General disorders
Fever
|
6.2%
5/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
General disorders
Lethargy
|
3.8%
3/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Gastrointestinal disorders
Vomiting
|
7.5%
6/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Gastrointestinal disorders
Stomatitis/Esophagitis
|
28.7%
23/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Hepatobiliary disorders
Hepatotoxicity
|
18.8%
15/80 • March 2000 to December 2004 (4 years, 8 months)
|
|
Hepatobiliary disorders
Elevated alanine aminotransferase
|
33.8%
27/80 • March 2000 to December 2004 (4 years, 8 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place