Myelodysplastic SyndromePhase 3NCT00469144
IV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome
A Phase 3 study testing Busulfan and Fludarabine in people with Myelodysplastic Syndrome and Leukemia, 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 giving busulfan in a dose based on blood levels, along with a fixed (unchanging) dose of fludarabine, is more effective and causes fewer side effects for AML or myelodysplastic syndrome patients than the standard method of giving a fixed busulfan dose based on… Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Myelodysplastic Syndrome, Leukemia, Acute Myeloid Leukemia
- What is being tested?
- Busulfan and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 233 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Nov 2014
- Phase
- Phase 3
- 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 Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Acute myeloid leukemia past first remission, in first or subsequent relapse, in first remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures. Only myeloid leukemia but not biphenotypic leukemia is allowed on this study.
- Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score
- Patient has not been administered any other systemic chemotherapeutic drug (including Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or day -9 for the test-dose arm of the study). Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study).
- No active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
- age <=65
- Patients must have a matched related or unrelated donor willing to donate. A donor who is HLA identical or mismatched in 1 locus on Class I [HLA, A or B], or molecularly mismatched in 1 locus on Class II [HLA, DR or DQ] is also acceptable.
Show all 17Show fewer
- ZUBROD performance status <2
- Life expectancy is not severely limited by concomitant illness and expected to be >12 weeks.
- Left ventricular ejection fraction >45% No uncontrolled arrhythmias or symptomatic cardiac disease.
- No symptomatic pulmonary disease. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary function will be assessed per pediatric BMT routine
- Serum creatinine </= 1.5 mg%.
- Serum glutamate pyruvate transaminase (SGPT) </= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
- No effusion or ascites >1L prior to drainage.
- HIV-negative.
- Female patient is not pregnant (negative B-human chorionic gonadotropin (HCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine).
- Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
- No prior autologous stem cell transplants
Who cannot join
- 1) None.
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 Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)
The goal of this clinical research study is to learn if giving busulfan in a dose based on blood levels, along with a fixed (unchanging) dose of fludarabine, is more effective and causes fewer side effects for AML or myelodysplastic syndrome patients than the standard method of giving a fixed busulfan dose based on body size, along with a fixed dose of fludarabine. The safety of dosing based on blood levels will also be studied.
Read the detailed description
Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA, and is commonly used in stem cell transplantation. Fludarabine is an antimetabolite drug which has anti-leukemia and immunosuppressive effects.
If you are eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 study groups. One group will receive a fixed dose of busulfan, while the other group will receive an adjusted dose of busulfan based on blood levels of the drug. Both groups will receive fludarabine treatment as well as a stem cell transplant.
Patients in the adjusted-dose group will first receive a low-level "test" dose of busulfan to check how their blood levels change over time; this information will be used to decide the next dose needed to reach the target blood level that matches your body size. Patients in the fixed-dose group will receive a fixed dose of busulfan without the test dose. If you are assigned to the fixed-dose group, this measurement will only affect your dose level if you have an unusually high or low drug level in your blood. Patients in both groups will have a total of about 20 teaspoons (less than 7 tablespoons) of blood drawn over time to check their busulfan blood levels following one or more of the busulfan treatments.
About 11 samples of blood will be drawn to check your blood levels of busulfan over time following the test dose and the first high-dose busulfan treatment; each sample is about 1 teaspoon of blood. A heparin lock will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for these blood level tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose.
Both groups of patients receive fludarabine through a central venous catheter (CVC--a small tube inserted into one of your major veins, usually in the chest or shoulder blade) over 1 hour, once a day, for 4 days. After each dose of fludarabine, the high-dose Busulfan will be infused through the CVC over 3 hours. These drugs are given to try to kill malignant cells and suppress your immune system in order to reduce the risk of stem cell transplant rejection. If you are going to be receiving a transplant from an HLA-type-nonidentical or unrelated donor, you will also receive Thymoglobulin (ATG) over 4 hours on the 3 days prior to the transplant to further suppress your immune system.
After 2 days of rest, the allogeneic stem cells (bone marrow or peripheral blood stem cells) will then be given intravenously (IV--through a needle in your vein). You will receive the drug G-CSF (Neupogen) as an injection under the skin daily starting 1 week after the transplant until your blood cell levels return to normal.
Patients usually remain in the hospital for about 4 weeks after stem cell transplantation. After you are released from the hospital, you will continue as an outpatient in the hospital area to be monitored for infections and transplant-related complications for a minimum of 100 days after the transplant.
Patients who previously had leukemia involvement in the nervous system may need to receive spinal taps, with injection of cytosine arabinoside and hydrocortisone, several times over the year after transplantation to try to keep the leukemia from coming back.
You will undergo blood tests and bone marrow biopsies at 3, 6, and 12 months after the transplant, to check if the disease is in remission. Your health status will be followed along with their local physician to find out if the leukemia or myelodysplastic syndrome comes back, as well as to check the length of your survival.
This is an investigational study. All of the drugs used in this study are approved by the FDA for treatment of cancer. Up to 230 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Myelodysplastic Syndrome, Leukemia, Acute Myeloid Leukemia
- Being tested
- Busulfan, Fludarabine
- Keywords
- Stem Cell Transplantation, Leukemia, Busulfan, Fludarabine, MDS, AML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days.
Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day.
Proceeding dosage level determined by pharmacokinetic studies to achieve a daily area under curve (AUC) of 6,000 microMol-min ± 10%.
FludarabineDrug
40 mg/m^2 IV Daily Over 1 Hour x 4 Days
| Study group | Role | What they receive |
|---|---|---|
| Fixed-Dose Busulfan + Fludarabine | Experimental | Busulfan Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days. Fludarabine 40 mg/m^2 IV Daily Over 1 Hour x 4 Days. Receives: Drug: Busulfan; Drug: Fludarabine |
| Adjusted Dose Busulfan + Fludarabine | Experimental | Busulfan Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day. Fludarabine 40 mg/m^2 IV Daily Over 1 Hour x 4 Days. Receives: Drug: Busulfan; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related Mortality (TRM)
Time to failure (TTF) defined as either disease recurrence or death, from the time of bone marrow transplant (BMT) and reported as TRM at 100 days and 1 year.
Treatment period defined as BMT Day -9 for patients treated on the PK-guided treatment arm, and day -7 for patients receiving the fixed-dose busulfan treatment through BMT Day +28. The post study surveillance period is defined as BMT Day +29 through BMT Day +100. Bone marrow aspirate with cytogenetics at approximately one (1) month and three (3) months, or as clinically indicated.
Response Criteria is measured by the bone marrow aspirate to determine it has leukemic blast. Bone marrow blast less than 5% is considered to be a complete response.
Measured: From transplant at Day 0 to Day 100 and 1 year following transplant
3 Year Progression Free Survival
PFS defined as length of time either due to disease recurrence or death, from the time of stem cell infusion (Bone marrow or PBPC) to 3 years.
Response Criteria is measured by the bone marrow aspirate to determine it has leukemic blast. Bone marrow blast less than 5% is considered to be a complete response.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2007 (estimated)
- Study startJun 2005
- Primary completionNov 2014
- Study completionNov 2014
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 Myelodysplastic 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Richard E. Champlin, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00469144
- Sponsor's protocol ID
- 2005-0366
- Other IDs
- NCI-2012-01475, CA55164
- Status last verified
- Jan 2021
- First submitted
- 3 May 2007
- Last updated
- 19 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT00469144
- Acronym / sponsor ID
- 2005-0366
- Conditions
- Myelodysplastic Syndrome, Leukemia, Acute Myeloid Leukemia
- Keywords
- Stem Cell Transplantation, Leukemia, Busulfan, Fludarabine, MDS, AML
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 233 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2005
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 4 May 2007 (estimated)
- Results
- Posted 19 Jan 2021
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 giving busulfan in a dose based on blood levels, along with a fixed (unchanging) dose of fludarabine, is more effective and causes fewer side effects for AML or myelodysplastic syndrome patients than the standard method of giving a fixed busulfan dose based on body size, along with a fixed dose of fludarabine. The safety of dosing based on blood levels will also be studied.
Detailed description
Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA, and is commonly used in stem cell transplantation. Fludarabine is an antimetabolite drug which has anti-leukemia and immunosuppressive effects.
If you are eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 study groups. One group will receive a fixed dose of busulfan, while the other group will receive an adjusted dose of busulfan based on blood levels of the drug. Both groups will receive fludarabine treatment as well as a stem cell transplant.
Patients in the adjusted-dose group will first receive a low-level "test" dose of busulfan to check how their blood levels change over time; this information will be used to decide the next dose needed to reach the target blood level that matches your body size. Patients in the fixed-dose group will receive a fixed dose of busulfan without the test dose. If you are assigned to the fixed-dose group, this measurement will only affect your dose level if you have an unusually high or low drug level in your blood. Patients in both groups will have a total of about 20 teaspoons (less than 7 tablespoons) of blood drawn over time to check their busulfan blood levels following one or more of the busulfan treatments.
About 11 samples of blood will be drawn to check your blood levels of busulfan over time following the test dose and the first high-dose busulfan treatment; each sample is about 1 teaspoon of blood. A heparin lock will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for these blood level tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose.
Both groups of patients receive fludarabine through a central venous catheter (CVC--a small tube inserted into one of your major veins, usually in the chest or shoulder blade) over 1 hour, once a day, for 4 days. After each dose of fludarabine, the high-dose Busulfan will be infused through the CVC over 3 hours. These drugs are given to try to kill malignant cells and suppress your immune system in order to reduce the risk of stem cell transplant rejection. If you are going to be receiving a transplant from an HLA-type-nonidentical or unrelated donor, you will also receive Thymoglobulin (ATG) over 4 hours on the 3 days prior to the transplant to further suppress your immune system.
After 2 days of rest, the allogeneic stem cells (bone marrow or peripheral blood stem cells) will then be given intravenously (IV--through a needle in your vein). You will receive the drug G-CSF (Neupogen) as an injection under the skin daily starting 1 week after the transplant until your blood cell levels return to normal.
Patients usually remain in the hospital for about 4 weeks after stem cell transplantation. After you are released from the hospital, you will continue as an outpatient in the hospital area to be monitored for infections and transplant-related complications for a minimum of 100 days after the transplant.
Patients who previously had leukemia involvement in the nervous system may need to receive spinal taps, with injection of cytosine arabinoside and hydrocortisone, several times over the year after transplantation to try to keep the leukemia from coming back.
You will undergo blood tests and bone marrow biopsies at 3, 6, and 12 months after the transplant, to check if the disease is in remission. Your health status will be followed along with their local physician to find out if the leukemia or myelodysplastic syndrome comes back, as well as to check the length of your survival.
This is an investigational study. All of the drugs used in this study are approved by the FDA for treatment of cancer. Up to 230 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fixed-Dose Busulfan + Fludarabine | Experimental | Drug: Busulfan, Drug: FludarabineBusulfan Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days. Fludarabine 40 mg/m^2 IV Daily Over 1 Hour x 4 Days. |
| Adjusted Dose Busulfan + Fludarabine | Experimental | Drug: Busulfan, Drug: FludarabineBusulfan Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day. Fludarabine 40 mg/m^2 IV Daily Over 1 Hour x 4 Days. |
Who may qualify
- Ages
- Up to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Acute myeloid leukemia past first remission, in first or subsequent relapse, in first remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures. Only myeloid leukemia but not biphenotypic leukemia is allowed on this study.
- Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score
- Patient has not been administered any other systemic chemotherapeutic drug (including Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or day -9 for the test-dose arm of the study). Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study).
- No active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
- age <=65
Key exclusion criteria (1 listed)
- 1) None.
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 |
|---|---|---|
| BusulfanFixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days. Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day. Proceeding dosage level determined by pharmacokinetic studies to achieve a daily area under curve (AUC) of 6,000 microMol-min ± 10%. | Drug | Adjusted Dose Busulfan + Fludarabine, Fixed-Dose Busulfan + Fludarabine |
| Fludarabine40 mg/m^2 IV Daily Over 1 Hour x 4 Days | Drug | Adjusted Dose Busulfan + Fludarabine, Fixed-Dose Busulfan + Fludarabine |
Primary outcome
Treatment-related Mortality (TRM)
Time frame: From transplant at Day 0 to Day 100 and 1 year following transplant
Time to failure (TTF) defined as either disease recurrence or death, from the time of bone marrow transplant (BMT) and reported as TRM at 100 days and 1 year. Treatment period defined as BMT Day -9 for patients treated on the PK-guided treatment arm, and day -7 for patients receiving the fixed-dose busulfan treatment through BMT Day +28. The post study surveillance period is defined as BMT Day +29 through BMT Day +100. Bone marrow aspirate with cytogenetics at approximately one (1) month and three (3) months, or as clinically indicated. Response Criteria is measured by the bone marrow aspirate to determine it has leukemic blast. Bone marrow blast less than 5% is considered to be a complete response.
3 Year Progression Free Survival
Time frame: 3 years
PFS defined as length of time either due to disease recurrence or death, from the time of stem cell infusion (Bone marrow or PBPC) to 3 years. Response Criteria is measured by the bone marrow aspirate to determine it has leukemic blast. Bone marrow blast less than 5% is considered to be a complete response.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2021.
- 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.
Richard E. Champlin, 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 3 study testing Busulfan and Fludarabine in people with Myelodysplastic Syndrome and Leukemia, 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 17 inclusion and 1 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 19 Jan 2021. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 19 Jan 2021). 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?
Treatment-related Mortality (TRM) (time frame: From transplant at Day 0 to Day 100 and 1 year following transplant). 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 19 Jan 2021.