Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01564277
• Other study ID #: I 197711
• Secondary ID: NCI-2011-03231I
• Status: Terminated
• Phase: Phase 2
• First received: March 2, 2012
• Last updated: December 11, 2017
• Start date: September 29, 2011
• Est. completion date: May 28, 2016

Study information

• Verified date: December 2017
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: May 28, 2016
• Est. primary completion date: May 28, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• 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)
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Burkitt Lymphoma
• Contiguous Stage II Adult Burkitt Lymphoma
• de Novo Myelodysplastic Syndromes
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Myelodysplastic Syndromes
• Noncontiguous Stage II Adult Burkitt Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• 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
• Syndrome
• Untreated Adult Acute Lymphoblastic Leukemia
• Untreated Adult Acute Myeloid Leukemia

Intervention

Drug:
• rasburicase
Given IV
• allopurinol
Given PO

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Within 24 hours of rasburicase treatment
Secondary	Number of Patients Requiring Additional Doses of Rasburicase to Maintain a Uric Acid Level =< 7.5mg/dL	Count of partcicpants requiring additional doses of rasburicase to maintain a uric acid level =< 7.5mg/dL by treatment arm.	Up to day 7
Secondary	Baseline White Blood Cell Count by Response	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).	Up to day 7
Secondary	Area Under the Plasma Uric Acid Concentration-time Curve (AUC) From Baseline (Day 1) to Day 7	The mean area under the plasma uric acid concentration-time curve (AUC) from baseline (Day 1) to Day 7	Up to day 7
Secondary	Safety of Low Single-doses of Rasburicase.	The number of patients with any adverse events .	up to day 7
Secondary	Number of Patients Experiencing a Doubling of Serum Creatinine	Count of participants experiencing a doubling of serum creatinine	up to day 6