NCT00513474

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2008

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 6, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 8, 2007

Completed
5 months until next milestone

Study Start

First participant enrolled

January 1, 2008

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 12, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 12, 2013

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

April 11, 2017

Completed
Last Updated

May 25, 2017

Status Verified

April 1, 2017

Enrollment Period

5.1 years

First QC Date

August 6, 2007

Results QC Date

February 27, 2017

Last Update Submit

April 20, 2017

Conditions

Keywords

graft versus host diseaseanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomarecurrent adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult Hodgkin lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult T-cell leukemia/lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent mycosis fungoides/Sezary syndromerecurrent small lymphocytic lymphomasplenic marginal zone lymphomaWaldenström macroglobulinemiarecurrent adult acute lymphoblastic leukemiarefractory chronic lymphocytic leukemiarecurrent adult acute myeloid leukemiaadult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult 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 leukemiablastic phase chronic myelogenous leukemiachronic phase chronic myelogenous leukemiarelapsing chronic myelogenous leukemiapreviously treated myelodysplastic syndromesprimary myelofibrosisatypical chronic myeloid leukemia, BCR-ABL1 negativechronic eosinophilic leukemiachronic myelomonocytic leukemiade novo myelodysplastic syndromesmyelodysplastic/myeloproliferative neoplasm, unclassifiablerefractory hairy cell leukemiarefractory multiple myelomasecondary acute myeloid leukemiasecondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Grades II to IV Acute Graft-Versus-Host Disease (aGVHD)

    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.

    Up to 71 months

Secondary Outcomes (3)

  • Uric Acid Levels

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

  • Number of Participant With Adverse Events (AE)

    Up to 71 months

  • Graft-versus-host and Host-versus-graft Immune Responses

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

Study Arms (2)

Rasburicase Group

EXPERIMENTAL

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: busulfanDrug: cyclophosphamideDrug: cyclosporin-ADrug: etoposideDrug: methotrexateDrug: rasburicaseDrug: sirolimusDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiationDrug: fludarabine

Control Group

OTHER

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: busulfanDrug: cyclophosphamideDrug: cyclosporin-ADrug: etoposideDrug: methotrexateDrug: sirolimusDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiationDrug: fludarabineDrug: allopurinol

Interventions

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

Control GroupRasburicase Group

Cyclophosphamide as standard of care for myeloablative conditioning at the investigator's discretion

Control GroupRasburicase Group

Cyclosporin-A as standard of care for GVHD prophylaxis at the investigator's discretion

Control GroupRasburicase Group

Etoposide as standard of care for myeloablative conditioning at the investigator's discretion

Control GroupRasburicase Group

Methotrexate 1.5 mg/kg/day on days -3, -2, and -1 as standard of care for GVHD prophylaxis at the investigator's discretion

Control GroupRasburicase Group

Rasburicase 0.20 mg/kg intravenous infusion over 30 minutes for 5 to 7 days

Rasburicase Group

Sirolimus as standard of care for GVHD prophylaxis at the investigator's discretion

Control GroupRasburicase Group

Tacrolimus as standard of care for GVHD prophylaxis at the investigator's discretion

Control GroupRasburicase Group
Control GroupRasburicase Group
Control GroupRasburicase Group

Total body irradiation 13.2 Gy over 8 fractions from day -7 to day - 4 for myeloablative conditioning at the investigator's discretion

Control GroupRasburicase Group

Fludarabine 40 mg/m\^2/day from day -6 to day -3 as myeloablative conditioning at the investigator's discretion

Control GroupRasburicase Group

Allopurinol per institutional guidelines

Control Group

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114-2617, United States

Location

Related Publications (1)

  • Yeh AC, Brunner AM, Spitzer TR, Chen YB, Coughlin E, McAfee S, Ballen K, Attar E, Caron M, Preffer FI, Yeap BY, Dey BR. Phase I study of urate oxidase in the reduction of acute graft-versus-host disease after myeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014 May;20(5):730-4. doi: 10.1016/j.bbmt.2014.02.003. Epub 2014 Feb 12.

MeSH Terms

Conditions

Myeloproliferative DisordersGraft vs Host DiseaseLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom MacroglobulinemiaLeukemia, Myeloid, AcuteCongenital AbnormalitiesLeukemia, Myeloid, Accelerated PhaseBlast CrisisLeukemia, Myeloid, Chronic-PhasePrimary MyelofibrosisLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativePdgfra-Associated Chronic Eosinophilic LeukemiaLeukemia, Myelomonocytic, ChronicLeukemia, Hairy Cell

Interventions

BusulfanCyclophosphamideCyclosporinsEtoposideMethotrexaterasburicaseSirolimusTacrolimusPeripheral Blood Stem Cell TransplantationWhole-Body IrradiationfludarabineAllopurinol

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesImmune System DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoma, T-CellLymphadenopathyLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, LymphoidLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, MyeloidCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, Myelogenous, Chronic, BCR-ABL PositiveCell Transformation, NeoplasticCarcinogenesisNeoplastic Processes

Intervention Hierarchy (Ancestors)

Butylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicGlucosidesGlycosidesCarbohydratesAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsMacrolidesLactonesHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeRadiotherapyInvestigative TechniquesPurines

Results Point of Contact

Title
Bimalangshu R. Dey, MD, PhD
Organization
Massachusetts General Hospital

Study Officials

  • Bimalangshu R. Dey, MD, PhD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

August 6, 2007

First Posted

August 8, 2007

Study Start

January 1, 2008

Primary Completion

February 12, 2013

Study Completion

February 12, 2013

Last Updated

May 25, 2017

Results First Posted

April 11, 2017

Record last verified: 2017-04

Locations