Tumor Lysis SyndromePhase 2NCT00628628
Rasburicase in Patients at Risk for Tumor Lysis Syndrome
A Phase 2 study testing As Needed Rasburicase and Fixed Dose Rasburicase in people with Tumor Lysis Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objectives: To determine the efficacy of rasburicase administered as a single dose followed by as needed dosing (investigational arm) as compared to fixed dosing for 5 days (standard treatment arm) in the treatment of patients at high risk or potential risk for tumor lysis syndrome. Secondary Objectives: 1. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tumor Lysis Syndrome
- What is being tested?
- As Needed Rasburicase and Fixed Dose Rasburicase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to May 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with hematological malignancies (leukemia/lymphoma) at high risk or potential risk for tumor lysis syndrome. High risk: hyperuricemia of malignancy (Uric acid levels >7.5); diagnosis of very aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia, chronic myelocytic 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) (continued on #2)
- (continued from # 1) 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 (ULN); Stage III-IV disease; Stage I-II disease with at least 1 lymph node/tumor >5cm in diameter.
- ECOG performance status 0-3
- Life expectancy >3 months
- Negative pregnancy test (females of child bearing potential) within </=2 weeks 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/Ethics Committee) obtained prior to study entry
Who cannot join
- Patient receiving any investigational drug for hyperuricemia within 30 days of planned first treatment with rasburicase
- Pregnancy or lactation
- Known history of significant allergy problem or documented history of asthma or asthmatic bronchitis
- Known history of glucose-6-phosphate dehydrogenase deficiency
- Known history of hemolysis and methemoglobinemia
- Previous therapy with urate oxidase
Show all 9Show fewer
- Other 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Study of Rasburicase Administered by Two Different Schedules (Fixed Dosing vs. As Needed Dosing) in Patients at High Risk or Potential Risk for Tumor Lysis Syndrome
Primary Objectives:
To determine the efficacy of rasburicase administered as a single dose followed by as needed dosing (investigational arm) as compared to fixed dosing for 5 days (standard treatment arm) in the treatment of patients at high risk or potential risk for tumor lysis syndrome.
Secondary Objectives:
- To evaluate the plasma uric acid area under the curve (AUC) from baseline through 7 days
- To evaluate the incidence of renal insufficiency and electrolyte abnormalities.
- To determine the safety and immunogenicity of rasburicase.
- To evaluate the cost-effectiveness of the experimental treatment (investigational arm).
Read the detailed description
The Study Drug and TLS Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the start of chemotherapy. A high level of uric acid in the blood may lead to decreased kidney function or kidney failure.
TLS occurs when high uric acid levels are caused by breakdown of tumor cells during the start of chemotherapy. The dead tumor cells can release uric acid and cause other symptoms of kidney failure, such as releasing large amounts of potassium and phosphorus (chemicals) into the blood.
Screening Tests Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study.
Your complete medical history will be recorded. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight.
Blood will be drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (using a sample from the routine blood draw) or urine pregnancy test.
Study Groups If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. There is an equal chance of being in either group.
Group A Participants in Group A will receive rasburicase by vein, over 30 minutes, on Day 1 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood. During Days 2-5 of Cycle 1 of chemotherapy, you will only receive rasburicase (once a day) if the levels of uric acid are high that day.
Group B Participants in Group B will receive rasburicase by vein, over 30 minutes, once a day from Days 1-5 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood.
Both Groups Treatment with rasburicase will only be given in Cycle 1 of chemotherapy. The chemotherapy will be given at least 4 hours (up to 24 hours) after the first dose of rasburicase.
Length of Study When your blood test results show that you do not have antibodies to rasburicase, your participation in this study will be over. You will be taken off this study if the TLS gets worse or intolerable side effects occur.
This is an investigational study. Rasburicase is commercially available, but it is not FDA approved for treating TLS. It is FDA approved for pediatric patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy that is expected to increase the blood levels of uric acid (the result of cancer cells dying from treatment). For treating TLS in adult patients, it has been authorized for use in research only. Up to 80 evaluable patients will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Tumor Lysis Syndrome
- Being tested
- As Needed Rasburicase, Fixed Dose Rasburicase
- Keywords
- Tumor Lysis Syndrome, TLS, hyperuricemia, Leukemia, Lymphoma, Acute myeloid leukemia, Chronic myelocytic leukemia, CML, lactate dehydrogenase, LDH, Myelodysplastic Syndrome, Rasburicase, Elitek™
- Medical subject headings
- Tumor Lysis Syndrome, Hyperuricemia, Leukemia, Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
As Needed RasburicaseDrug
Also called Elitek™
.15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed.
Fixed Dose RasburicaseDrug
Also called Elitek™
.15 mg/kg IV Over 30 Minutes Daily
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. Receives: Drug: As Needed Rasburicase |
| Group B | Experimental | Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily Receives: Drug: Fixed Dose Rasburicase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Plasma Uric Acid (UA) Response
Plasma UA response is defined as normalization of plasma UA levels within 48 hours after the start of study drug (rasburicase) and maintaining within the normal range after the final drug infusion on day 5. Plasma samples for UA were collected at baseline before rasburicase, 4- and 24-hours post-rasburicase, and daily during treatment.
Measured: First cycle of chemotherapy, up to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2008 (estimated)
- Study startJan 2008
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tumor Lysis SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Saroj Vadhan-Raj, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00628628
- Sponsor's protocol ID
- 2006-0918
- Status last verified
- May 2013
- First submitted
- 25 Feb 2008
- Last updated
- 1 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Vadhan-Raj S, Fayad LE, Fanale MA, Pro B, Rodriguez A, Hagemeister FB, Bueso-Ramos CE, Zhou X, McLaughlin PW, Fowler N, Shah J, Orlowski RZ, Samaniego F, Wang M, Cortes JE, Younes A, Kwak LW, Sarlis NJ, Romaguera JE. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol. 2012 Jun;23(6):1640-5. doi: 10.1093/annonc/mdr490. Epub 2011 Oct 19.
PubMed 22015451
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Rasburicase Administered by Two Different Schedules (Fixed Dosing vs. As Needed Dosing) in Patients at High Risk or Potential Risk for Tumor Lysis Syndrome
- ClinicalTrials.gov ID
- NCT00628628
- Acronym / sponsor ID
- 2006-0918
- Conditions
- Tumor Lysis Syndrome
- Keywords
- Tumor Lysis Syndrome, TLS, hyperuricemia, Leukemia, Lymphoma, Acute myeloid leukemia, Chronic myelocytic leukemia, CML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Jan 2008
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 5 Mar 2008 (estimated)
- Results
- Posted 1 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
To determine the efficacy of rasburicase administered as a single dose followed by as needed dosing (investigational arm) as compared to fixed dosing for 5 days (standard treatment arm) in the treatment of patients at high risk or potential risk for tumor lysis syndrome.
Secondary Objectives:
- To evaluate the plasma uric acid area under the curve (AUC) from baseline through 7 days
- To evaluate the incidence of renal insufficiency and electrolyte abnormalities.
- To determine the safety and immunogenicity of rasburicase.
- To evaluate the cost-effectiveness of the experimental treatment (investigational arm).
Detailed description
The Study Drug and TLS Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the start of chemotherapy. A high level of uric acid in the blood may lead to decreased kidney function or kidney failure.
TLS occurs when high uric acid levels are caused by breakdown of tumor cells during the start of chemotherapy. The dead tumor cells can release uric acid and cause other symptoms of kidney failure, such as releasing large amounts of potassium and phosphorus (chemicals) into the blood.
Screening Tests Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study.
Your complete medical history will be recorded. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight.
Blood will be drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (using a sample from the routine blood draw) or urine pregnancy test.
Study Groups If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. There is an equal chance of being in either group.
Group A Participants in Group A will receive rasburicase by vein, over 30 minutes, on Day 1 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood. During Days 2-5 of Cycle 1 of chemotherapy, you will only receive rasburicase (once a day) if the levels of uric acid are high that day.
Group B Participants in Group B will receive rasburicase by vein, over 30 minutes, once a day from Days 1-5 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood.
Both Groups Treatment with rasburicase will only be given in Cycle 1 of chemotherapy. The chemotherapy will be given at least 4 hours (up to 24 hours) after the first dose of rasburicase.
Length of Study When your blood test results show that you do not have antibodies to rasburicase, your participation in this study will be over. You will be taken off this study if the TLS gets worse or intolerable side effects occur.
This is an investigational study. Rasburicase is commercially available, but it is not FDA approved for treating TLS. It is FDA approved for pediatric patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy that is expected to increase the blood levels of uric acid (the result of cancer cells dying from treatment). For treating TLS in adult patients, it has been authorized for use in research only. Up to 80 evaluable patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: As Needed RasburicaseAs Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. |
| Group B | Experimental | Drug: Fixed Dose RasburicaseFixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with hematological malignancies (leukemia/lymphoma) at high risk or potential risk for tumor lysis syndrome. High risk: hyperuricemia of malignancy (Uric acid levels >7.5); diagnosis of very aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia, chronic myelocytic 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) (continued on #2)
- (continued from # 1) 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 (ULN); Stage III-IV disease; Stage I-II disease with at least 1 lymph node/tumor >5cm in diameter.
- ECOG performance status 0-3
- Life expectancy >3 months
- Negative pregnancy test (females of child bearing potential) within </=2 weeks of rasburicase dose and use of efficient contraceptive method (both males and females). Pregnancy test may be performed on serum (HCG) or urine (HCG)
Key exclusion criteria (9 listed)
- Patient receiving any investigational drug for hyperuricemia within 30 days of planned first treatment with rasburicase
- Pregnancy or lactation
- Known history of significant allergy problem or documented history of asthma or asthmatic bronchitis
- Known history of glucose-6-phosphate dehydrogenase deficiency
- Known history of hemolysis and methemoglobinemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| As Needed RasburicaseAlso: Elitek™.15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. | Drug | Group A |
| Fixed Dose RasburicaseAlso: Elitek™.15 mg/kg IV Over 30 Minutes Daily | Drug | Group B |
Primary outcome
Number of Participants With Plasma Uric Acid (UA) Response
Time frame: First cycle of chemotherapy, up to 5 days
Plasma UA response is defined as normalization of plasma UA levels within 48 hours after the start of study drug (rasburicase) and maintaining within the normal range after the final drug infusion on day 5. Plasma samples for UA were collected at baseline before rasburicase, 4- and 24-hours post-rasburicase, and daily during treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22015451Vadhan-Raj S, Fayad LE, Fanale MA, Pro B, Rodriguez A, Hagemeister FB, Bueso-Ramos CE, Zhou X, McLaughlin PW, Fowler N, Shah J, Orlowski RZ, Samaniego F, Wang M, Cortes JE, Younes A, Kwak LW, Sarlis NJ, Romaguera JE. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol. 2012 Jun;23(6):1640-5. doi: 10.1093/annonc/mdr490. Epub 2011 Oct 19.
- MD Anderson Cancer CenterLink provided by the sponsor.
Related trials for Tumor Lysis Syndrome
Recruiting
Reassessment of the Risk of Hemolytic Syndrome in Patients With Chronic Lymphocytic Leukemia Treated With a Regimen Containing Venetoclax
Chronic Lymphoid Leukemia
RecruitingPhase 1
A Study of Lonitoclax (ZE50-0134) in Relapsed or Refractory B-cell Malignancies
CLL / SLL, CLL (Chronic Lymphocytic Leukemia)
RecruitingPhase 3
A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Chronic Lymphocytic Leukemia
RecruitingObservational study
Timing of Renal Replacement Therapy Initiation in Tumor Lysis Syndrome
Renal Replacement Therapy for Acute Kidney Injury in ICU
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saroj Vadhan-Raj, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing As Needed Rasburicase and Fixed Dose Rasburicase in people with Tumor Lysis Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Plasma Uric Acid (UA) Response (time frame: First cycle of chemotherapy, up to 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00628628, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2013.