Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed by Allopurinol in Adult Patients With Malignancy

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01564277

Enrollment

Registered

2012-03-27

Start date

2011-09-29

Completion date

2016-05-28

Last updated

2018-01-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

DRUGrasburicase

Given IV

DRUGallopurinol

Given PO

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Probability of Obtaining a Uric Acid Level =< 7.5mg/dL	Within 24 hours of rasburicase treatment	The proportion of patients able to achieve and/or maintain a uric acid level =\< 7.5mg/dL for each treatment arm.

Secondary

Measure	Time frame	Description
Number of Patients Requiring Additional Doses of Rasburicase to Maintain a Uric Acid Level =< 7.5mg/dL	Up to day 7	Count of partcicpants requiring additional doses of rasburicase to maintain a uric acid level =\< 7.5mg/dL by treatment arm.
Baseline White Blood Cell Count by Response	Up to day 7	The mean baseline white blood cell count of patients with a complete response (CR) (patients who achieved uric acid level =\< 7.5mg/dL) and no CR (patients with uric acid level \> 7.5mg/dL).
Area Under the Plasma Uric Acid Concentration-time Curve (AUC) From Baseline (Day 1) to Day 7	Up to day 7	The mean area under the plasma uric acid concentration-time curve (AUC) from baseline (Day 1) to Day 7
Safety of Low Single-doses of Rasburicase.	up to day 7	The number of patients with any adverse events .
Number of Patients Experiencing a Doubling of Serum Creatinine	up to day 6	Count of participants experiencing a doubling of serum creatinine

Countries

United States

Participant flow

Participants by arm

Arm	Count
Arm I (1.5mg Rasburicase) Patients receive 1.5mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6. rasburicase: Given IV allopurinol: Given PO	12
Arm II (3 mg Rasburicase) Patients receive 3 mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6. rasburicase: Given IV allopurinol: Given PO	12
Total	24

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Physician Decision	1	0
Overall Study	Protocol Violation	0	1

Baseline characteristics

Characteristic	Arm I (1.5mg Rasburicase)	Arm II (3 mg Rasburicase)	Total
Age, Categorical <=18 years	0 Participants	1 Participants	1 Participants
Age, Categorical >=65 years	8 Participants	7 Participants	15 Participants
Age, Categorical Between 18 and 65 years	4 Participants	4 Participants	8 Participants
Age, Continuous	69.9 years STANDARD_DEVIATION 7.5	68.4 years STANDARD_DEVIATION 16.4	69.2 years STANDARD_DEVIATION 12.3
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	0 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	9 Participants	12 Participants	21 Participants
Sex: Female, Male Female	4 Participants	6 Participants	10 Participants
Sex: Female, Male Male	8 Participants	6 Participants	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	12 / 12	11 / 12
serious Total, serious adverse events	0 / 12	1 / 12

Outcome results

Primary

Probability of Obtaining a Uric Acid Level =< 7.5mg/dL

The proportion of patients able to achieve and/or maintain a uric acid level =\< 7.5mg/dL for each treatment arm.

Time frame: Within 24 hours of rasburicase treatment