Trial Outcomes & Findings for Rasburicase in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer or Other Disease Undergoing Donor Stem Cell Transplant (NCT NCT00513474)

Last Updated: 2017-05-25

Results Overview

aGVHD severity was determined using International Bone Marrow Transplant Registry (IBMTR) scale stage and grade of the skin, liver and gut. Stage 1: Skin=maculopapular rash \<25% of body surface; Liver=Bilirubin 2-3 mg/dL and Gut=500-999 mL diarrhea/day or peristent nausea with histologic evidence of GvHD. Stage 2: Skin=maculopapular rash 25-50% of body surface; Liver=Bilirubin 3.1-6 mg/dL and Gut=1000-1499 mL diarrhea/day. Stage 3: Skin=maculopapular rash \>50% of body surface; Liver=Bilirubin 6.1-15 mg/dL and Gut=≥1500 mL diarrhea/day. Stage 4: Skin=generalized erythroderma with bulla formation; Liver=Bilirubin \>15 mg/dL and Gut=severe abdominal pain. Grade 1: Stage 1-2 rash; no liver or gut involvement. Grade II: Stage 3 rash, or stage 1 liver involvement, or stage 1 gut involvement. Grade III: None to stage 3 skin rash with stage 2-3 liver, or stage 2-4 gut involvement. Grade IV: Stage 4 skin rash, or stage 4 liver involvement.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

46 participants

Primary outcome timeframe

Up to 71 months

Results posted on

2017-05-25

Participant Flow

Participant milestones

Participant milestones
Measure	Rasburicase Group Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Overall Study STARTED	25	21
Overall Study Received Rasburicase Per Protocol	24	0
Overall Study COMPLETED	18	12
Overall Study NOT COMPLETED	7	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Rasburicase Group Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Overall Study Death	6	9
Overall Study Participant Withdrew Consent	1	0

Baseline Characteristics

Rasburicase in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer or Other Disease Undergoing Donor Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rasburicase Group n=21 Participants Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group n=21 Participants Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.	Total n=42 Participants Total of all reporting groups
Age, Continuous	42.9 years n=5 Participants	45 years n=7 Participants	44 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Graft-Versus-Host Disease (GVHD) Prophylaxis Intervention MRD: Cyclsporine + Methotrexate	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Graft-Versus-Host Disease (GVHD) Prophylaxis Intervention MRD: Tacrolimus + Methotrexate	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Graft-Versus-Host Disease (GVHD) Prophylaxis Intervention MUD: Tacrolimus + Methotrexate + ATG	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Graft-Versus-Host Disease (GVHD) Prophylaxis Intervention MUD: Tacrolimus + Methotrexate	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Conditioning Protocol Interventions Busulfan + Cyclophosphamide	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Conditioning Protocol Interventions Busulfan + Fludarabine	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Conditioning Protocol Interventions Total Body Irradiation + Cyclophosphamide	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 71 months

Population: Intent-to-treat participants included in the analyses.

Outcome measures

Outcome measures
Measure	Rasburicase Group n=21 Participants Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group n=21 Participants Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Percentage of Participants With Grades II to IV Acute Graft-Versus-Host Disease (aGVHD)	24 percentage of participants	57 percentage of participants

SECONDARY outcome

Timeframe: Pre-transplant Day -7 to Day -1 and Post-transplant Day 0 to Day 6

Population: Intent-to-treat population with data available for analyses.

Blood was collected and analyzed at a laboratory for serum uric acid levels reported in milligrams(mg)/deciliter(dL). Data is presented for those participants who experienced Grade II to IV aGVHD and those participants who did not experience Grade II to IV aGVHD at pre-transplant and post-transplant.

Outcome measures

Outcome measures
Measure	Rasburicase Group n=21 Participants Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group n=21 Participants Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Uric Acid Levels Day -4	0.1 mg/dL Standard Deviation 0.324	2.579 mg/dL Standard Deviation 1.249
Uric Acid Levels Day -3	0.067 mg/dL Standard Deviation 0.2	2.358 mg/dL Standard Deviation 1.21
Uric Acid Levels Day 0	0.938 mg/dL Standard Deviation 0.887	2.163 mg/dL Standard Deviation 1.012
Uric Acid Levels Day 1	1.624 mg/dL Standard Deviation 1.205	2.671 mg/dL Standard Deviation 1.056
Uric Acid Levels Day 5	2.595 mg/dL Standard Deviation 1.729	2.579 mg/dL Standard Deviation 1.318
Uric Acid Levels Day 6	2.705 mg/dL Standard Deviation 1.665	2.653 mg/dL Standard Deviation 1.33
Uric Acid Levels Day -7	0.1 mg/dL Standard Deviation 0.209	4.157 mg/dL Standard Deviation 1.886
Uric Acid Levels Day -6	0.075 mg/dL Standard Deviation 0.199	3.419 mg/dL Standard Deviation 1.752
Uric Acid Levels Day -5	0.086 mg/dL Standard Deviation 0.24	2.967 mg/dL Standard Deviation 1.437
Uric Acid Levels Day -2	0.081 mg/dL Standard Deviation 0.15	1.867 mg/dL Standard Deviation 1.097
Uric Acid Levels Day -1	0.438 mg/dL Standard Deviation 0.611	1.71 mg/dL Standard Deviation 0.931
Uric Acid Levels Day 2	2.076 mg/dL Standard Deviation 1.37	2.778 mg/dL Standard Deviation 0.985
Uric Acid Levels Day 3	2.271 mg/dL Standard Deviation 1.303	2.805 mg/dL Standard Deviation 1.028
Uric Acid Levels Day 4	2.548 mg/dL Standard Deviation 1.454	2.758 mg/dL Standard Deviation 1.161

SECONDARY outcome

Timeframe: Up to 71 months

Population: Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Rasburicase Group n=21 Participants Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group n=21 Participants Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Number of Participant With Adverse Events (AE)	21 Participants	21 Participants

SECONDARY outcome

Timeframe: Days -2, 0, and Days 14, 21 and 35 days post-transplant

Population: Due to laboratory and budgetary issues the planned laboratory testing and assays were not performed and no data were collected.

Laboratory tests such as limited dilution assay (LDA) were to be performed to assess graft-versus-host and host-versus-graft immune responses.

Outcome measures

Outcome data not reported

Adverse Events

Rasburicase Group

Serious events: 10 serious events

Other events: 21 other events

Deaths: 0 deaths

Control Group

Serious events: 9 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rasburicase Group n=21 participants at risk Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group n=21 participants at risk Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Nervous system disorders Seizure	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Immune system disorders Engraftment syndrome	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Vascular disorders Venoocclusive disease	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Blood and lymphatic system disorders Relapsed disease	33.3% 7/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	33.3% 7/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Infections and infestations Infection from aGVHD flare	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Infections and infestations Respiratory failure	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Infections and infestations H1N1 influenza	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Infections and infestations Metapneumovirus	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.

Other adverse events

Other adverse events
Measure	Rasburicase Group n=21 participants at risk Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.	Control Group n=21 participants at risk Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Gastrointestinal disorders Vomiting	61.9% 13/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	52.4% 11/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
General disorders Fever	23.8% 5/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	42.9% 9/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Gastrointestinal disorders Nausea	90.5% 19/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	90.5% 19/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Gastrointestinal disorders Diarrhea	71.4% 15/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	42.9% 9/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
General disorders Mucositis	95.2% 20/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	81.0% 17/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Skin and subcutaneous tissue disorders Rash	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	9.5% 2/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Metabolism and nutrition disorders Edema	23.8% 5/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	9.5% 2/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Gastrointestinal disorders Tongue numbness	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Blood and lymphatic system disorders Thrombocytopenia	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Blood and lymphatic system disorders Hemolytic anemia	4.8% 1/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.	0.00% 0/21 • Up to 71 months Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.

Additional Information

Bimalangshu R. Dey, MD, PhD

Massachusetts General Hospital

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place