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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00513474
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Duration (Months): 61.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

RATIONALE: Rasburicase may be an effective treatment for graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This clinical trial is studying how well rasburicase works in preventing graft-versus-host disease in patients with hematologic cancer or other disease undergoing donor stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms	Drug: busulfan; Drug: cyclophosphamide; Drug: cyclosporin-A; Drug: etoposide; Drug: methotrexate; Drug: rasburicase; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation; Drug: fludarabine; Drug: allopurinol	Phase 1

Detailed Description

OBJECTIVES:

Primary

• To evaluate the incidence and severity of acute graft-vs-host disease (GVHD) in rasburicase-treated patients who will undergo myeloablative human leukocyte antigen (HLA)-matched related or unrelated donor allogeneic peripheral blood hematopoietic stem cell transplantation (SCT) for hematologic malignancies and compare these outcomes with those of historical controls.

Secondary

• To evaluate the efficacy (in terms of reduction of uric acid levels) and safety of rasburicase in patients undergoing myeloablative allogeneic SCT.

• To evaluate the graft-versus-host and host-versus-graft immune responses in rasburicase-treated patients.

OUTLINE: This is a multicenter study.

Patients receive a conventional myeloablative conditioning regimen consisting of high doses of cyclophosphamide, busulfan, and etoposide, with or without total-body irradiation. Depending on the preparative regimen selected, the conditioning of recipients will take a total of 6 to 7 days. On day 0, patients will receive filgrastim (G-CSF)-mobilized HLA-matched, related, or unrelated donor allogeneic peripheral blood stem cells (unmanipulated). Patients will receive standard graft-vs-host disease prophylaxis consisting of cyclosporine or tacrolimus and methotrexate or sirolimus. Patients will receive rasburicase IV over 30 minutes, beginning on the first day of conditioning therapy, for 5 consecutive days. If after 5 days of rasburicase the patient's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.

Blood is obtained on day 0 and then at 14, 28, and 42 days post-transplant for immunologic studies, including quantitative analysis to follow the recovery of T cells, B cells, natural killer cells, dendritic cells (DC), and monocytes using flow cytometry (FCM); phenotypic analysis of T cells, DC and monocytes by FCM; lymphocyte activation analysis: CD3, CD4, CD8, CD25 2. CD3, CD8, CD71, CD69; DC analysis: CD45, CD14, DR, CD86, CD80 2. CD45, CD14, CD40, CD11c; and in vitro functional studies such as mixed lymphocyte reaction (MLR) and cell-mediated lysis (CML) to assess for the graft-versus-host and host-versus-graft responses. Peripheral blood is collected for chimerism studies on days 28 and 100 post-transplant.

After completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Rasburicase to Prevent Graft -Versus-Host Disease
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Feb 12, 2013
• Actual Study Completion Date: Feb 12, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: busulfan; Busulfan 3.2 mg/kg/day from day -7 to day -4 as standard of care for myeloablative (bone marrow depletion) conditioning at the investigator's discretion; Drug: cyclophosphamide; Cyclophosphamide as standard of care for myeloablative conditioning at the investigator's discretion; Drug: cyclosporin-A; Cyclosporin-A as standard of care for GVHD prophylaxis at the investigator's discretion; Drug: etoposide; Etoposide as standard of care for myeloablative conditioning at the investigator's discretion; Drug: methotrexate; Methotrexate 1.5 mg/kg/day on days -3, -2, and -1 as standard of care for GVHD prophylaxis at the investigator's discretion; Drug: rasburicase; Rasburicase 0.20 mg/kg intravenous infusion over 30 minutes for 5 to 7 days; Drug: sirolimus; Sirolimus as standard of care for GVHD prophylaxis at the investigator's discretion; Drug: tacrolimus; Tacrolimus as standard of care for GVHD prophylaxis at the investigator's discretion; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation; Total body irradiation 13.2 Gy over 8 fractions from day -7 to day - 4 for myeloablative conditioning at the investigator's discretion; Drug: fludarabine; Fludarabine 40 mg/m^2/day from day -6 to day -3 as myeloablative conditioning at the investigator's discretion
Other: 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.	Drug: busulfan; Busulfan 3.2 mg/kg/day from day -7 to day -4 as standard of care for myeloablative (bone marrow depletion) conditioning at the investigator's discretion; Drug: cyclophosphamide; Cyclophosphamide as standard of care for myeloablative conditioning at the investigator's discretion; Drug: cyclosporin-A; Cyclosporin-A as standard of care for GVHD prophylaxis at the investigator's discretion; Drug: etoposide; Etoposide as standard of care for myeloablative conditioning at the investigator's discretion; Drug: methotrexate; Methotrexate 1.5 mg/kg/day on days -3, -2, and -1 as standard of care for GVHD prophylaxis at the investigator's discretion; Drug: sirolimus; Sirolimus as standard of care for GVHD prophylaxis at the investigator's discretion; Drug: tacrolimus; Tacrolimus as standard of care for GVHD prophylaxis at the investigator's discretion; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation; Total body irradiation 13.2 Gy over 8 fractions from day -7 to day - 4 for myeloablative conditioning at the investigator's discretion; Drug: fludarabine; Fludarabine 40 mg/m^2/day from day -6 to day -3 as myeloablative conditioning at the investigator's discretion; Drug: allopurinol; Allopurinol per institutional guidelines

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Grades II to IV Acute Graft-Versus-Host Disease (aGVHD) [Up to 71 months]

   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.

Secondary Outcome Measures

1. Uric Acid Levels [Pre-transplant Day -7 to Day -1 and Post-transplant Day 0 to Day 6]

   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.

2. Number of Participant With Adverse Events (AE) [Up to 71 months]

   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.

3. Graft-versus-host and Host-versus-graft Immune Responses [Days -2, 0, and Days 14, 21 and 35 days post-transplant]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Patients with hematologic malignancies for whom conventional myeloablative allogeneic stem cell transplantation is deemed clinically appropriate and who are eligible for conventional myeloablative allogeneic stem cell transplantation on treatment plans/protocols, including any of the following:

• Non-Hodgkin lymphoma or Hodgkin lymphoma (relapsed or refractory disease)

• Chronic lymphocytic leukemia (received more than one previous treatment regimen)

• Acute myelogenous or lymphoblastic leukemia (AML/ALL) (high-risk disease, in first complete remission [CR1] or subsequent remission, or primary refractory disease)

• Chronic myelogenous leukemia in tyrosine-kinase resistant chronic phase, accelerated or blast phase, or primary refractory disease

• Myelodysplastic syndromes in International Prognostic Scoring System (IPSS) high-intermediate or high-risk groups

• Other hematologic disorders for which allogeneic stem cell transplantation is appropriate (e.g., myelofibrosis)

• Patients who have relapsed after standard autologous and/or allogeneic bone marrow transplant are eligible

• Must be receiving filgrastim (G-CSF)-mobilized related or unrelated donor allogeneic peripheral blood stem cells

• Patients receiving hematopoietic stem cells of any other sources such as a marrow graft or umbilical cord blood will not be eligible for this study

• Donor must be HLA-genotypically or phenotypically 6 of 6 antigen matched (at the A, B, DR loci) related or unrelated

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Patients with a "currently active" second malignancy other than non-melanoma skin cancers can only be registered if survival from the second malignancy is expected to be more than 1 year

• Ejection fraction ≥ 45% by either radioisotope Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO)

• Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) ≥ 50% of predicted with no symptomatic pulmonary disease

• Mini Mental Status Exam Score ≥ 20

• Patients must have an expected life expectancy of at least 3 months

• Patients with symptomatic visceral, blood stream or nervous system opportunistic infection are eligible if the infection has been appropriately treated and controlled

• Patients with a fungal infection must have had treatment for at least one month and must have proof of regression of the infection prior to enrollment

• Patients may be on antibiotics at the time of transplant

Exclusion criteria:

• Human Immunodeficiency Virus (HIV) infection

• Uncontrolled diabetes mellitus

• Active congestive heart failure from any cause

• Previous history of congestive heart failure allowed

• Active angina pectoris

• Oxygen-dependent obstructive pulmonary disease

• Failure to demonstrate adequate compliance with medical therapy and follow-up

• Known history of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency or history of hemolysis indicative of G6PD deficiency

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114-2617

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Bimalangshu R. Dey, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bimalangshu Dey, Associate Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00513474
• Other Study ID Numbers: CDR0000558480; MGH-07-071; DFCI-07-071
• First Posted: Aug 8, 2007
• Last Update Posted: May 25, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Bimalangshu Dey, Associate Professor of Medicine, Massachusetts General Hospital: graft versus host disease; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult T-cell leukemia/lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent small lymphocytic lymphoma; splenic marginal zone lymphoma; Waldenström macroglobulinemia; recurrent adult acute lymphoblastic leukemia; refractory chronic lymphocytic leukemia; recurrent adult acute myeloid leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; previously treated myelodysplastic syndromes; primary myelofibrosis; atypical chronic myeloid leukemia, BCR-ABL1 negative; chronic eosinophilic leukemia; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; refractory hairy cell leukemia; refractory multiple myeloma; secondary acute myeloid leukemia; secondary myelodysplastic syndromes
• Additional relevant MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Syndrome; Cyclosporine; Sirolimus; Cyclophosphamide; Busulfan; Methotrexate; Fludarabine; Etoposide; Allopurinol; Rasburicase; Tacrolimus; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Rasburicase Group	Control Group
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	25	21
Received Rasburicase Per Protocol	24	0
COMPLETED	18	12
NOT COMPLETED	7	9

Baseline Characteristics

Arm/Group Title	Rasburicase Group	Control Group	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	21	21	42
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	42.9	45	44
Sex: Female, Male (Count of Participants)
Female	7 33.3%	12 57.1%	19 45.2%
Male	14 66.7%	9 42.9%	23 54.8%
Graft-Versus-Host Disease (GVHD) Prophylaxis Intervention (Count of Participants)
MRD: Cyclsporine + Methotrexate	14 66.7%	11 52.4%	25 59.5%
MRD: Tacrolimus + Methotrexate	2 9.5%	2 9.5%	4 9.5%
MUD: Tacrolimus + Methotrexate + ATG	4 19%	8 38.1%	12 28.6%
MUD: Tacrolimus + Methotrexate	1 4.8%	2 9.5%	3 7.1%
Conditioning Protocol Interventions (Count of Participants)
Busulfan + Cyclophosphamide	12 57.1%	16 76.2%	28 66.7%
Busulfan + Fludarabine	2 9.5%	0 0%	2 4.8%
Total Body Irradiation + Cyclophosphamide	7 33.3%	5 23.8%	12 28.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Grades II to IV Acute Graft-Versus-Host Disease (aGVHD)
Description	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.
Time Frame	Up to 71 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat participants included in the analyses.

Arm/Group Title	Rasburicase Group	Control Group
Arm/Group Description	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.	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.
Measure Participants	21	21
Number [percentage of participants]	24 114.3%	57 271.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasburicase Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.036
	Comments
	Method	Gray's test for competing risks
	Comments

2. Secondary Outcome

Title	Uric Acid Levels
Description	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.
Time Frame	Pre-transplant Day -7 to Day -1 and Post-transplant Day 0 to Day 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rasburicase Group	Control Group
Arm/Group Description	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.	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.
Measure Participants	21	21
Day -7	0.1 (0.209)	4.157 (1.886)
Day -6	0.075 (0.199)	3.419 (1.752)
Day -5	0.086 (0.24)	2.967 (1.437)
Day -4	0.1 (0.324)	2.579 (1.249)
Day -3	0.067 (0.2)	2.358 (1.21)
Day -2	0.081 (0.15)	1.867 (1.097)
Day -1	0.438 (0.611)	1.71 (0.931)
Day 0	0.938 (0.887)	2.163 (1.012)
Day 1	1.624 (1.205)	2.671 (1.056)
Day 2	2.076 (1.37)	2.778 (0.985)
Day 3	2.271 (1.303)	2.805 (1.028)
Day 4	2.548 (1.454)	2.758 (1.161)
Day 5	2.595 (1.729)	2.579 (1.318)
Day 6	2.705 (1.665)	2.653 (1.33)

3. Secondary Outcome

Title	Number of Participant With Adverse Events (AE)
Description	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.
Time Frame	Up to 71 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rasburicase Group	Control Group
Arm/Group Description	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.	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.
Measure Participants	21	21
Count of Participants [Participants]	21 100%	21 100%

4. Secondary Outcome

Title	Graft-versus-host and Host-versus-graft Immune Responses
Description	Laboratory tests such as limited dilution assay (LDA) were to be performed to assess graft-versus-host and host-versus-graft immune responses.
Time Frame	Days -2, 0, and Days 14, 21 and 35 days post-transplant

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rasburicase Group	Control Group
Arm/Group Description	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.	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.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 71 months
Adverse Event Reporting Description	Safety population included all participants who received at least one dose of protocol specified treatment and were in remission at the time of transplant.
Arm/Group Title	Rasburicase Group		Control Group
Arm/Group Description	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.		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.
All Cause Mortality
	Rasburicase Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rasburicase Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/21 (47.6%)		9/21 (42.9%)
Blood and lymphatic system disorders
Relapsed disease	7/21 (33.3%)		7/21 (33.3%)
Immune system disorders
Engraftment syndrome	1/21 (4.8%)		0/21 (0%)
Infections and infestations
Infection from aGVHD flare	0/21 (0%)		1/21 (4.8%)
Respiratory failure	0/21 (0%)		1/21 (4.8%)
H1N1 influenza	1/21 (4.8%)		0/21 (0%)
Metapneumovirus	1/21 (4.8%)		0/21 (0%)
Nervous system disorders
Seizure	1/21 (4.8%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/21 (4.8%)		0/21 (0%)
Vascular disorders
Venoocclusive disease	1/21 (4.8%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Rasburicase Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		21/21 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/21 (4.8%)		0/21 (0%)
Hemolytic anemia	1/21 (4.8%)		0/21 (0%)
Gastrointestinal disorders
Vomiting	13/21 (61.9%)		11/21 (52.4%)
Nausea	19/21 (90.5%)		19/21 (90.5%)
Diarrhea	15/21 (71.4%)		9/21 (42.9%)
Tongue numbness	1/21 (4.8%)		0/21 (0%)
General disorders
Fever	5/21 (23.8%)		9/21 (42.9%)
Mucositis	20/21 (95.2%)		17/21 (81%)
Metabolism and nutrition disorders
Edema	5/21 (23.8%)		2/21 (9.5%)
Skin and subcutaneous tissue disorders
Rash	1/21 (4.8%)		2/21 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.