LeukemiaPhase 2NCT01200485
Rasburicase in Patients at High Risk for Tumor Lysis Syndrome (TLS) During Cycle-2
A Phase 2 study testing Rasburicase and Allopurinol in people with Leukemia and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- What is being tested?
- Rasburicase and Allopurinol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Jul 2016
- 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 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Randomized Phase 2 Study to Evaluate the Efficacy of Rasburicase in Patients at Risk for TLS During Two Cycles of Chemotherapy
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.
Read the detailed description
Study Drugs:
Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the beginning of chemotherapy. A high level of uric acid results from TLS and can lead to kidney failure.
Allopurinol is designed to help block uric acid. It is the standard of care for helping to control increased uric acid levels caused by TLS.
Study Groups and Drug Administration:
Each cycle will last about 3 weeks.
If you are found to be eligible to take part in this study, you will receive rasburicase by vein over about 30 minutes on Day 1 of Cycle 1 (about 4 hours before you begin receiving chemotherapy). If the doctor thinks it is needed, you may also receive the drug on Days 2-5 of Cycle 1.
For Cycle 2, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. There is an equal chance of being assigned to either group:
- If you are in Group A, you will receive rasburicase on Day 1 of Cycle 2. If the doctor thinks it is needed, you may also receive the drug on Days 2-5 of Cycle 2.
- If you are in Group B, you will receive allopurinol by vein over 30 minutes each day on Days 1-5 of Cycle 2.
Group B Participants: If your uric acid blood levels continue to increase in Cycle 2 and you show symptoms of tumor lysis syndrome, you may receive rasburicase as a single dose. If the doctor thinks it is needed, you may also receive 1 or more additional dose(s).
Study Visits:
On Day 1 of Cycle 1:
- Blood (about 1 teaspoon) will be drawn to check uric acid levels before and 4 hours after you receive rasburicase.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be drawn for antibody testing. Antibodies are proteins made by the body that the immune system uses to help prevent disease.
On Days 2-5 of Cycle 1:
- Blood (about 1 teaspoon) will be drawn to check uric acid levels.
- Blood (about 2 tablespoon) will be drawn for routine tests.
At the end of both cycles, blood (about 1 teaspoon) will be drawn for antibody testing.
Length of Study:
You will receive drugs on this study for up to 2 cycles. You will be taken off study if intolerable side effects occur.
Your participation in the study will be over after the follow-up visit.
Follow-Up:
Three (3) months after the end of Cycle 2, blood (about 1 teaspoon) will be drawn for antibody testing.
This is an investigational study. Allopurinol is commercially available and FDA approved to treat TLS. Rasburicase is commercially available and FDA approved for treating TLS for 1 cycle in patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy. It is investigational to give rasburicase for 2 cycles.
Up to 55 patients will take part in this study. All will be enrolled at MD Anderson.
- Being tested
- Rasburicase, Allopurinol
- Keywords
- Supportive Care, Recombinant urate oxidase, Chemotherapy, Tumor Lysis Syndrome (TLS), Hematologic malignancies, Acute myeloid leukemia
- Medical subject headings
- Leukemia, Lymphoma, Tumor Lysis Syndrome, Hematologic Neoplasms, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RasburicaseDrug
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.
AllopurinolDrug
Also called Loprin, Zurinol, Zyloprim
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Rasburicase |
| Arm B (Allopurinol) | Experimental | Participants randomized to Allopurinol (300 mg/day) by vein each day on Days 1-5 of Cycle 2. Receives: Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Up to 24 hours of cycle 2 dose delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2010 (estimated)
- Study startApr 2011
- Primary completionJul 2016
- Study completionJul 2016
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.
- Other trials for LeukemiaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 55 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
- NCT01200485
- Sponsor's protocol ID
- 2010-0284
- Other IDs
- NCI-2012-01889
- Status last verified
- Jan 2020
- First submitted
- 9 Sep 2010
- Last updated
- 31 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Study to Evaluate the Efficacy of Rasburicase in Patients at Risk for TLS During Two Cycles of Chemotherapy
- ClinicalTrials.gov ID
- NCT01200485
- Acronym / sponsor ID
- 2010-0284
- Keywords
- Supportive Care, Recombinant urate oxidase, Chemotherapy, Tumor Lysis Syndrome (TLS), Hematologic malignancies, Acute myeloid leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Apr 2011
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 13 Sep 2010 (estimated)
- Results
- Posted 31 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Drugs:
Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the beginning of chemotherapy. A high level of uric acid results from TLS and can lead to kidney failure.
Allopurinol is designed to help block uric acid. It is the standard of care for helping to control increased uric acid levels caused by TLS.
Study Groups and Drug Administration:
Each cycle will last about 3 weeks.
If you are found to be eligible to take part in this study, you will receive rasburicase by vein over about 30 minutes on Day 1 of Cycle 1 (about 4 hours before you begin receiving chemotherapy). If the doctor thinks it is needed, you may also receive the drug on Days 2-5 of Cycle 1.
For Cycle 2, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. There is an equal chance of being assigned to either group:
- If you are in Group A, you will receive rasburicase on Day 1 of Cycle 2. If the doctor thinks it is needed, you may also receive the drug on Days 2-5 of Cycle 2.
- If you are in Group B, you will receive allopurinol by vein over 30 minutes each day on Days 1-5 of Cycle 2.
Group B Participants: If your uric acid blood levels continue to increase in Cycle 2 and you show symptoms of tumor lysis syndrome, you may receive rasburicase as a single dose. If the doctor thinks it is needed, you may also receive 1 or more additional dose(s).
Study Visits:
On Day 1 of Cycle 1:
- Blood (about 1 teaspoon) will be drawn to check uric acid levels before and 4 hours after you receive rasburicase.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be drawn for antibody testing. Antibodies are proteins made by the body that the immune system uses to help prevent disease.
On Days 2-5 of Cycle 1:
- Blood (about 1 teaspoon) will be drawn to check uric acid levels.
- Blood (about 2 tablespoon) will be drawn for routine tests.
At the end of both cycles, blood (about 1 teaspoon) will be drawn for antibody testing.
Length of Study:
You will receive drugs on this study for up to 2 cycles. You will be taken off study if intolerable side effects occur.
Your participation in the study will be over after the follow-up visit.
Follow-Up:
Three (3) months after the end of Cycle 2, blood (about 1 teaspoon) will be drawn for antibody testing.
This is an investigational study. Allopurinol is commercially available and FDA approved to treat TLS. Rasburicase is commercially available and FDA approved for treating TLS for 1 cycle in patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy. It is investigational to give rasburicase for 2 cycles.
Up to 55 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rasburicase Alone | Experimental | Drug: RasburicaseRasburicase 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). |
| Arm A (Rasburicase) | Experimental | Drug: RasburicaseParticipants randomized to Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2. |
| Arm B (Allopurinol) | Experimental | Drug: AllopurinolParticipants randomized to Allopurinol (300 mg/day) by vein each day on Days 1-5 of Cycle 2. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
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 |
|---|---|---|
| RasburicaseCycle 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. | Drug | Arm A (Rasburicase), Rasburicase Alone |
| AllopurinolAlso: Loprin, Zurinol, ZyloprimArm 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. | Drug | Arm B (Allopurinol) |
Primary outcome
Number of Participants (Incidence) of LTLS (Laboratory Tumor Lysis Syndrome)
Time frame: Up to two 3-week cycles, 6 weeks
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.
Number of Cycle 2 Participants Normalizing Uric Acid Levels (UAL) Within 24 Hours of Treatment
Time frame: Up to 24 hours of cycle 2 dose delivery
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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 Rasburicase and Allopurinol in people with Leukemia and Lymphoma, 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 4 inclusion and 10 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 31 Jan 2020. 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 31 Jan 2020). 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 (Incidence) of LTLS (Laboratory Tumor Lysis Syndrome) (time frame: Up to two 3-week cycles, 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jan 2020.