Trial Outcomes & Findings for High-Dose Cyclophosphamide for Steroid Refractory GVHD (NCT NCT00492921)

NCT ID: NCT00492921

Last Updated: 2018-09-14

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: Day 28
• Results posted on: 2018-09-14

Participant Flow

Participant milestones

Measure	Cyclophosphamide 50 mg/kg Treatment with cyclophosphamide 50 mg/kg/d x 1 day.	Cyclophosphamide 100 mg/kg Treatment with cyclophosphamide 50 mg/kg/d x 2 days.	Cyclophosphamide 150 mg/kg Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
Overall Study STARTED	5	4	3
Overall Study COMPLETED	4	4	2
Overall Study NOT COMPLETED	1	0	1

Reasons for withdrawal

Measure	Cyclophosphamide 50 mg/kg Treatment with cyclophosphamide 50 mg/kg/d x 1 day.	Cyclophosphamide 100 mg/kg Treatment with cyclophosphamide 50 mg/kg/d x 2 days.	Cyclophosphamide 150 mg/kg Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
Overall Study Death	1	0	1

Baseline Characteristics

High-Dose Cyclophosphamide for Steroid Refractory GVHD

Baseline characteristics by cohort

Measure	Cyclophosphamide n=12 Participants Treatment with cyclophosphamide 50 mg/kg/d x 2 days, then dose adjusted according to continuous reassessment model according to toxicities until MTD found.
Age, Categorical <=18 years	1 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	38 years n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	7 Participants n=93 Participants
Region of Enrollment United States	12 Participants n=93 Participants

PRIMARY outcome

Timeframe: Day 28

Outcome measures

Measure	Cyclophosphamide 50 mg/kg n=5 Participants Treatment with cyclophosphamide 50 mg/kg/d x 1 day.	Cyclophosphamide 100 mg/kg n=4 Participants Treatment with cyclophosphamide 50 mg/kg/d x 2 days.	Cyclophosphamide 150 mg/kg n=3 Participants Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide	4 Participants	4 Participants	2 Participants

PRIMARY outcome

Timeframe: Day 28

Population: This analysis excludes the two participants who died early because their responses were not assessed prior to death.

Percentage of patients whose GVHD (as defined by Przepiorka criteria) responded to cyclophosphamide (complete response). Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

Outcome measures

Measure	Cyclophosphamide 50 mg/kg n=4 Participants Treatment with cyclophosphamide 50 mg/kg/d x 1 day.	Cyclophosphamide 100 mg/kg n=4 Participants Treatment with cyclophosphamide 50 mg/kg/d x 2 days.	Cyclophosphamide 150 mg/kg n=2 Participants Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
GVHD Response Rate	1 Participants	0 Participants	1 Participants

Adverse Events

Cyclophosphamide 50 mg/kg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 3 deaths

Cyclophosphamide 100 mg/kg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 3 deaths

Cyclophosphamide 150 mg/kg

Serious events: 3 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Measure	Cyclophosphamide 50 mg/kg n=5 participants at risk Treatment with cyclophosphamide 50 mg/kg/d x 1 day.	Cyclophosphamide 100 mg/kg n=4 participants at risk Treatment with cyclophosphamide 50 mg/kg/d x 2 days.	Cyclophosphamide 150 mg/kg n=3 participants at risk Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
Cardiac disorders Hypotension	0.00% 0/5 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	0.00% 0/4 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	33.3% 1/3 • Number of events 1 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.
Infections and infestations Pneumonia	0.00% 0/5 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	0.00% 0/4 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	33.3% 1/3 • Number of events 1 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.
Gastrointestinal disorders Pain - abdomen	0.00% 0/5 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	0.00% 0/4 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	33.3% 1/3 • Number of events 1 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/5 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	25.0% 1/4 • Number of events 1 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.	0.00% 0/3 • every week through Day 30 The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Javier Bolanos Meade

JHU SKCCC

Phone: 410-614-6398

Email: Fbolano2@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place