MyelofibrosisPhase 2NCT00475020
Allogeneic Stem Cell Transplantation for Myelofibrosis and Myelodysplastic Syndrome
A Phase 2 study testing Busulfan, Fludarabine and Thymoglobulin (ATG) in people with Myelofibrosis, 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 a combination of fludarabine, busulfan, and antithymocyte globulin (ATG) can help to control myelofibrosis or myelodysplastic syndrome in patients receiving a bone marrow or blood stem cell transplant. The safety of these drugs will also be studied. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Myelofibrosis
- What is being tested?
- Busulfan, Fludarabine and Thymoglobulin (ATG)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2006to 4 Oct 2017
- 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 Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with Idiopathic Myelofibrosis or Myelofibrosis secondary to Polycythemia Vera or Essential Thrombocythemia or Myelodysplastic syndrome with or without fibrosis.
- Patients 75 years or younger
- Patients must have an HLA matched or at least a 9/10 antigen (A, B, C, DQ or DR) matched related or unrelated donor.
- Patients must have a Zubrod PS 2 or less.
- Creatinine < 1.6 mg/dl
- Ejection fraction >/= 40%, unless cleared by cardiology
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- Serum direct bilirubin < 2 mg/dl (unless due to Gilbert's syndrome), serum glutamate pyruvate transaminase (SGPT) </= 4 x normal values
- Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), or diffusing capacity of lung for carbon monoxide (DLCO) >/= 40% of expected.
- Negative Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
Who cannot join
- Uncontrolled life-threatening infections
- HIV positive
- Patients with Active viral hepatitis
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: Allogeneic Stem Cell Transplantation for Myelofibrosis and Myelodysplastic Syndrome Using Reduced Intensity Busulfan and Fludarabine Conditioning
The goal of this clinical research study is to learn if using a combination of fludarabine, busulfan, and antithymocyte globulin (ATG) can help to control myelofibrosis or myelodysplastic syndrome in patients receiving a bone marrow or blood stem cell transplant. The safety of these drugs 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 transplants. Fludarabine is a drug that has anti-leukemia and immunosuppressive effects. ATG helps to reduce the risk of transplant rejection and to prevent graft versus host disease.
You will receive fludarabine by vein over 1 hour on Days -5 to -2. You will receive busulfan by vein over 3 hours on Day -5 to -2 immediately after completing fludarabine. If you have an unrelated or a mismatched donor, you will receive ATG by vein over 6 hours on Days -3 to -1 to prevent graft versus host disease and to help engraftment.
You will first receive a low-level "test" dose of busulfan, and blood samples (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) tests. This may be done as an outpatient prior to inpatient admission. PK tests measure the level of the study drug in the blood over different time points. This information will be used to decide the next dose needed to reach the target blood level that matches your body size.
About 11 total samples of blood will be drawn for PK testing after the test dose and before the first high-dose busulfan treatment. 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 or for any other reason, you will receive the standard fixed busulfan dose without the "test dose."
You will receive the donor bone marrow or blood stem cells by vein over about 1 hour on Day 0.
Two (2) days before the stem cell infusion on Day -2, tacrolimus will be started as a non-stop infusion by vein and will be changed to oral tablets before you leave the hospital. You will continue to take tacrolimus by mouth, for at least 4 months.
Four (4) doses of Methotrexate will be give as a short infusion Day 1, Day 3, Day 6 and Day 11 after stem cell infusion. Both these are given to decrease the risk of getting graft-vs-host disease (GvHD). Further immunosuppressive therapy with methylprednisolone (a steroid) or other drugs may also be used to treat GvHD if it occurs.
You will have 3 teaspoonfuls of blood drawn for routine tests every day while you are in the hospital and at least 2 times a week for the first 100 days after transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if you get a fever. Three (3) teaspoonful of blood and a bone marrow aspirate and biopsy will be taken 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months after the transplant to check the response to the treatment. After the first 2 years, your disease status will be followed by a yearly phone call or letter from you or your regular doctor to the study doctor.
Tests and/or procedures may be performed before the scheduled time, if your doctor thinks it is needed.
You will be taken off the study if your disease gets worse or if further treatment is not in your best interest.
This is an investigational study. All the drugs to be used in this study are FDA approved and commercially available. About 110 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Myelofibrosis
- Being tested
- Busulfan, Fludarabine, Thymoglobulin (ATG)
- Keywords
- Idiopathic Myelofibrosis, Myelofibrosis, Essential Thrombocythemia, Polycythemia Vera, Busulfan, Antithymocyte Globulin, ATG, Fludarabine, Thymoglobulin
- Medical subject headings
- Primary Myelofibrosis, Thrombocythemia, Essential, Polycythemia Vera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex, Myleran
Test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days
FludarabineDrug
Also called Fludarabine Phosphate
40 mg/m^2 by vein daily over 1 hour x 4 days
Thymoglobulin (ATG)Drug
Also called Antithymocyte Globulin, Thymoglobulin, ATG
2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine + Busulfan + Thymoglobulin | Experimental | Fludarabine 40 mg/m^2 by vein daily over 1 hour x 4 days. Busulfan test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days. Thymoglobulin 2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor. Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Thymoglobulin (ATG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Non-relapse Mortality at 100 Days Post-transplant
To evaluate the safety of Fludarabine/Busulfan as conditioned regimen for allogeneic stem cell transplantation in patients with myelofibrosis/myelodysplastic syndrome at 100 days post-transplant
Measured: Non-relapse mortality at 100 days post-transplant
Secondary outcomes (1)
Efficacy of This Therapy 3 Years Post-transplant
Efficacy Assessed as Number of Participants with Overall Survival, Leukemia Progression, Primary Graft Failure and Complete Hematological Response. Primary graft failure is defined as failure to achieve an ANC >/= 0.5 x 10 (9)/L for 3 consecutive days and evidence of donor chimerism by Day +28. Complete hematological response is defined by hemoglobin >/= 120 g/L; or achievement of transfusion independence, with stable Hb > 110 g/L, for RBC transfusion-dependent participants; Spleen not palpable; platelet count 150 x 10 (9)/L; White blood cell 4 x 10 (9)/L to 10 x 10(9)/L.
Measured: Up to 3 years post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2007 (estimated)
- Study start4 Jan 2006
- Primary completion4 Oct 2017
- Study completion4 Oct 2017
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 MyelofibrosisStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Uday Popat, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00475020
- Sponsor's protocol ID
- 2005-0726
- Other IDs
- NCI-2012-01477
- Status last verified
- May 2019
- First submitted
- 15 May 2007
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Stem Cell Transplantation for Myelofibrosis and Myelodysplastic Syndrome Using Reduced Intensity Busulfan and Fludarabine Conditioning
- ClinicalTrials.gov ID
- NCT00475020
- Acronym / sponsor ID
- 2005-0726
- Conditions
- Myelofibrosis
- Keywords
- Idiopathic Myelofibrosis, Myelofibrosis, Essential Thrombocythemia, Polycythemia Vera, Busulfan, Antithymocyte Globulin, ATG, Fludarabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 4 Jan 2006 (actual)
- Primary completion
- 4 Oct 2017 (actual)
- Study completion
- 4 Oct 2017 (actual)
- First posted
- 17 May 2007 (estimated)
- Results
- Posted 4 Dec 2018
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 a combination of fludarabine, busulfan, and antithymocyte globulin (ATG) can help to control myelofibrosis or myelodysplastic syndrome in patients receiving a bone marrow or blood stem cell transplant. The safety of these drugs 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 transplants. Fludarabine is a drug that has anti-leukemia and immunosuppressive effects. ATG helps to reduce the risk of transplant rejection and to prevent graft versus host disease.
You will receive fludarabine by vein over 1 hour on Days -5 to -2. You will receive busulfan by vein over 3 hours on Day -5 to -2 immediately after completing fludarabine. If you have an unrelated or a mismatched donor, you will receive ATG by vein over 6 hours on Days -3 to -1 to prevent graft versus host disease and to help engraftment.
You will first receive a low-level "test" dose of busulfan, and blood samples (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) tests. This may be done as an outpatient prior to inpatient admission. PK tests measure the level of the study drug in the blood over different time points. This information will be used to decide the next dose needed to reach the target blood level that matches your body size.
About 11 total samples of blood will be drawn for PK testing after the test dose and before the first high-dose busulfan treatment. 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 or for any other reason, you will receive the standard fixed busulfan dose without the "test dose."
You will receive the donor bone marrow or blood stem cells by vein over about 1 hour on Day 0.
Two (2) days before the stem cell infusion on Day -2, tacrolimus will be started as a non-stop infusion by vein and will be changed to oral tablets before you leave the hospital. You will continue to take tacrolimus by mouth, for at least 4 months.
Four (4) doses of Methotrexate will be give as a short infusion Day 1, Day 3, Day 6 and Day 11 after stem cell infusion. Both these are given to decrease the risk of getting graft-vs-host disease (GvHD). Further immunosuppressive therapy with methylprednisolone (a steroid) or other drugs may also be used to treat GvHD if it occurs.
You will have 3 teaspoonfuls of blood drawn for routine tests every day while you are in the hospital and at least 2 times a week for the first 100 days after transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if you get a fever. Three (3) teaspoonful of blood and a bone marrow aspirate and biopsy will be taken 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months after the transplant to check the response to the treatment. After the first 2 years, your disease status will be followed by a yearly phone call or letter from you or your regular doctor to the study doctor.
Tests and/or procedures may be performed before the scheduled time, if your doctor thinks it is needed.
You will be taken off the study if your disease gets worse or if further treatment is not in your best interest.
This is an investigational study. All the drugs to be used in this study are FDA approved and commercially available. About 110 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine + Busulfan + Thymoglobulin | Experimental | Drug: Busulfan, Drug: Fludarabine, Drug: Thymoglobulin (ATG)Fludarabine 40 mg/m^2 by vein daily over 1 hour x 4 days. Busulfan test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days. Thymoglobulin 2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor. |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with Idiopathic Myelofibrosis or Myelofibrosis secondary to Polycythemia Vera or Essential Thrombocythemia or Myelodysplastic syndrome with or without fibrosis.
- Patients 75 years or younger
- Patients must have an HLA matched or at least a 9/10 antigen (A, B, C, DQ or DR) matched related or unrelated donor.
- Patients must have a Zubrod PS 2 or less.
- Creatinine < 1.6 mg/dl
Key exclusion criteria (3 listed)
- Uncontrolled life-threatening infections
- HIV positive
- Patients with Active viral hepatitis
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 |
|---|---|---|
| BusulfanAlso: Busulfex, MyleranTest dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days | Drug | Fludarabine + Busulfan + Thymoglobulin |
| FludarabineAlso: Fludarabine Phosphate40 mg/m^2 by vein daily over 1 hour x 4 days | Drug | Fludarabine + Busulfan + Thymoglobulin |
| Thymoglobulin (ATG)Also: Antithymocyte Globulin, Thymoglobulin, ATG2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor | Drug | Fludarabine + Busulfan + Thymoglobulin |
Primary outcome
Rate of Non-relapse Mortality at 100 Days Post-transplant
Time frame: Non-relapse mortality at 100 days post-transplant
To evaluate the safety of Fludarabine/Busulfan as conditioned regimen for allogeneic stem cell transplantation in patients with myelofibrosis/myelodysplastic syndrome at 100 days post-transplant
1 secondary outcome
Efficacy of This Therapy 3 Years Post-transplant
Time frame: Up to 3 years post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- 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.
Uday Popat, 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 Busulfan, Fludarabine and Thymoglobulin (ATG) in people with Myelofibrosis, 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 9 inclusion and 3 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 21 May 2019. 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 4 Dec 2018). 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?
Rate of Non-relapse Mortality at 100 Days Post-transplant (time frame: Non-relapse mortality at 100 days post-transplant). 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 21 May 2019.