Rasburicase in Patients at High Risk for Tumor Lysis Syndrome (TLS) During Cycle-2

NCT01200485 | Completed Phase 2 Results DMC

• 2 other identifiers: 2010-0284NCI-2012-01889
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if using Elitek (rasburicase) for 2 cycles can help to control or prevent TLS better than 1 cycle of rasburicase and 1 cycle of allopurinol. The safety of this treatment will also be studied.

Conditions

Leukemia; Lymphoma

Keywords

Supportive Care; Recombinant urate oxidase; Chemotherapy; Tumor Lysis Syndrome (TLS); Hematologic malignancies; Acute myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants (Incidence) of LTLS (Laboratory Tumor Lysis Syndrome)

  Number of participants (incidence) of LTLS in the two arms, as defined by the Cairo-Bishop criteria , during cycle 2. Cairo-Bishop criteria: Uric acid x ≥ 476 μmol/l or 25% increase from baseline Potassium x ≥ 6·0 mmol/l or 25% increase from baseline Phosphorous x ≥ 2·1 mmol/l (children), x ≥1·45 mmol/l (adults) or 25% increase from baseline Calcium x ≤ 1·75 mmol/l or 25% decrease from baseline Laboratory tumour lysis syndrome (LTLS) is defined as either a 25% change or level above or below normal, as defined above, for any two or more serum values of uric acid, potassium, phosphate, and calcium within 3d before or 7d after the initiation of chemotherapy.

  Up to two 3-week cycles, 6 weeks

• Number of Cycle 2 Participants Normalizing Uric Acid Levels (UAL) Within 24 Hours of Treatment

  Number of participants with normalized UAL as determined by a uric acid blood test at either 24 hours. A uric acid blood test, also known as a serum uric acid measurement, determines how much uric acid is present in the blood where normal levels are 2.4-6.0 mg/dL (female) and 3.4-7.0 mg/dL (male).

  Up to 24 hours of cycle 2 dose delivery

Study Arms (3)

Rasburicase Alone

EXPERIMENTAL

Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1 (21 day cycle).

Drug: Rasburicase

Arm A (Rasburicase)

EXPERIMENTAL

Participants randomized to Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.

Drug: Rasburicase

Arm B (Allopurinol)

EXPERIMENTAL

Participants randomized to Allopurinol (300 mg/day) by vein each day on Days 1-5 of Cycle 2.

Drug: Allopurinol

Interventions

Rasburicase DRUG

Cycle 1: 3 mg/kg by vein on Day 1, plus as needed dosing (until day 5), during Cycle 1. Cycle 2 Arm A: 0.15 mg/kg by vein on Day 1 of Cycle 2, plus as needed dosing (until day 5), during Cycle 2.

Arm A (Rasburicase); Rasburicase Alone

Allopurinol DRUG

Arm B: 300 mg/day by vein, as standard of care, over 30 minutes each day on days 1-5 of cycle 2 in 21 day cycle.

Also known as: Loprin, Zurinol, Zyloprim

Arm B (Allopurinol)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients that are high risk for TLS or potential/intermediate risk for TLS as described below: (a) High risk: Hyperuricemia of malignancy (Uric acid levels \>7.5); or diagnosis of very aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia, CML in blast crisis; high grade myelodysplastic syndrome only if they have \>10% bone marrow blast involvement and given aggressive treatment similar to acute myeloid leukemia (AML). (b) Potential risk: Diagnosis of aggressive lymphoma/leukemia based on (REAL) classification. Plus one or more of the following criteria: lactate dehydrogenase (LDH) \>/= 2 x upper limit of normal (UNL); Stage III-IV disease; Stage I-II disease with at least 1 lymph node/tumor \> 5 cm in diameter. For patients with potential/intermediate risk for TLS- Only those planned to receive alternating regimens (or non-standard regimens) in 2 cycles (example; R-Hyper-central venous access device (CVAD) alternating with MTX/ARA-C) will be eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
• Negative pregnancy test (females of child bearing potential) within \</= 1 week of rasburicase dose and use of efficient contraceptive method (both males and females). Pregnancy test may be performed on serum (HCG) or urine (HCG).
• Signed written informed consent approved by the Institutional Review Board obtained prior to study entry.

You may not qualify if:

• Prior H/O severe allergy or asthma requiring active treatment.
• Patients with mantle cell lymphoma (MCL) with stage 1 or 2 disease.
• Patient receiving any investigational drug for hyperuricemia within 30 days of planned first treatment with rasburicase.
• Pregnancy or lactation.
• Known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Known history of hemolysis and/or methemoglobinemia.
• Previous therapy with urate oxidase.
• Conditions unsuitable for participation in the trial in the Investigator's opinion.
• Unwillingness to comply with the requirements of the protocol.
• Use of allopurinol within 72 hours of the study entry.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Sanofi: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Lymphoma; Tumor Lysis Syndrome; Hematologic Neoplasms; Leukemia, Myeloid, Acute

Interventions

rasburicase; Allopurinol

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Saroj Vadhan, MD/Professor, Cytokine & Supportive Oncology
• Organization: UT MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Saroj Vadhan-Raj, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 13, 2010
• Study Start: April 1, 2011
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Locations

US (1)