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Rasburicase to Prevent Graft -Versus-Host Disease


N/A
18 Years
65 Years
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

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Trial Information

Rasburicase to Prevent Graft -Versus-Host Disease


OBJECTIVES:

Primary

- To evaluate the incidence and severity of acute graft-vs-host disease (GVHD) in
rasburicase-treated patients who will undergo myeloablative 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.

Inclusion Criteria


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 IPSS (International Prognostic Scoring System)
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 MUGA scan or ECHO

- Lung 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:

- 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 G6PD deficiency or history of hemolysis indicative of G6PD
deficiency

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Incidence and severity of acute graft-vs-host disease

Principal Investigator

Bimalangshu R. Dey, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital

Authority:

Unspecified

Study ID:

CDR0000558480

NCT ID:

NCT00513474

Start Date:

January 2008

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • 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
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location
Massachusetts General Hospital Boston, Massachusetts  02114-2617