Clinical trial NCT01564277: Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies
Official title: Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed by Allopurinol in Adult Patients With Malignancy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
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)
Blastic Phase Chronic Myelogenous Leukemia
Contiguous Stage II Adult Burkitt Lymphoma
de Novo Myelodysplastic Syndromes
Noncontiguous Stage II Adult Burkitt Lymphoma
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Stage I Adult Burkitt Lymphoma
Stage III Adult Burkitt Lymphoma
Stage IV Adult Burkitt Lymphoma
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Myeloid Leukemia
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-03-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II trial studies how well giving rasburicase together with allopurinol works in treating patients with hematologic malignancies. Rasburicase may reduce the level of uric acid in the blood. Allopurinol may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known which dose of rasburicase is more effective in treating hematologic malignancies when given together with or without allopurinol.

Detailed description: PRIMARY OBJECTIVES:

I. To prospectively evaluate the efficacy, as defined by uric acid response rate, of 2 different single low doses of rasburicase followed by allopurinol in 2 treatment arms.

SECONDARY OBJECTIVES:

I. To estimate the proportion of patients requiring additional doses of rasburicase to maintain a uric acid level =\< 7.5mg/dL on day 2 through day 6.

II. To identify differential characteristics of the patients who do not respond to treatment.

III. To measure the area under the plasma uric acid concentration-time curve (AUC) from baseline (day 1) to day 7, time to plasma uric acid level less than or equal to 7.5mg/dL.

IV. To evaluate the rate of patients requiring hemodialysis (HD) V. To evaluate the safety of low single-doses of rasburicase. VI. To evaluate the rate of patients expressing a doubling of serum creatinine.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive 1.5mg of rasburicase intravenously (IV) over 30 minutes on day 1\* and allopurinol orally (PO) once daily (QD) on days 1-6.

ARM II: Patients receive 3 mg of rasburicase IV over 30 minutes on day 1\* and allopurinol PO QD on days 1-6.

NOTE: \*Patients with serum uric acid \>= 7.5mg/dl also receive rasburicase IV on days 2-3.

After completion of study treatment, patients are followed up at 30 days.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) status of 0-3
* Active leukemia and Burkitt leukemia/lymphoma treated in-house that puts them at risk for tumor lysis syndrome (TLS)
* Serum uric acid level \>= 7.5mg/dL and high risk for TLS as defined by:

  * A diagnosis of acute myeloid leukemia (AML), or
  * A diagnosis of blast-phase chronic myeloid leukemia (CML), or
  * A diagnosis of high-grade myelodysplastic syndrome (MDS) with \>= 10% blast bone marrow blast involvement, or
  * Acute lymphoblastic leukemia (ALL), or
  * Burkitt leukemia/lymphoma
* Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

* History of asthma
* History of severe or life threatening atopic allergy
* Hypersensitivity to uricases
* Known prior sensitivity to allopurinol
* Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Recent prior history of uricolytic therapy defined as therapy within the last 7 days

Primary outcomes:
measure: Probability of Obtaining a Uric Acid Level =< 7.5mg/dL
timeFrame: Within 24 hours of rasburicase treatment
Secondary outcomes:
measure: Number of Patients Requiring Additional Doses of Rasburicase to Maintain a Uric Acid Level =< 7.5mg/dL
timeFrame: Up to day 7
measure: Baseline White Blood Cell Count by Response
timeFrame: Up to day 7
measure: Area Under the Plasma Uric Acid Concentration-time Curve (AUC) From Baseline (Day 1) to Day 7
timeFrame: Up to day 7
measure: Safety of Low Single-doses of Rasburicase.
timeFrame: up to day 7
measure: Number of Patients Experiencing a Doubling of Serum Creatinine
timeFrame: up to day 6
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Eunice Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: