A Phase 2 interventional study of Busulfan and Fludarabine in Myelofibrosis, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged Up to 75 Years. Per ClinicalTrials.gov, last updated 2019-05-21.
Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment
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.
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.
1,317 studies on the registry are indexed under Preleukemia; 57 are open to participants now.
This study's enrollment of 63 is above the median of 36 across 1,060 interventional studies indexed under Preleukemia.
Browse Preleukemia studies →M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.
Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Drug: Busulfan · Drug: Fludarabine · Drug: Thymoglobulin (ATG)
Test dose = 32 mg/m\^2 by vein x 1 day; 100 mg/m\^2 by vein daily over 3 hours x 4 days
Also known as: Busulfex, Myleran
40 mg/m\^2 by vein daily over 1 hour x 4 days
Also known as: Fludarabine Phosphate
2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor
Also known as: Antithymocyte Globulin, Thymoglobulin, ATG
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
Time frame: Non-relapse mortality at 100 days post-transplant
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.
Time frame: Up to 3 years post-transplant
| Milestone | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| Started | 63 |
| Completed | 58 |
| Not completed | 5 |
| Withdrew: Physician decision | 3 |
| Withdrew: Insurance denial | 1 |
| Withdrew: Donor not able to donate the last minute | 1 |
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
| Participants | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| Infections | 1 |
| Organ Failures | 2 |
| Sudden death: likely due to ischemic cardiac event | 1 |
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.
| Participants | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| Overall survival at 3 years | 25 |
| Leukemia progression | 27 |
| Primary graft failures | 0 |
| Complete hematological remission | 44 |
Collected over January 2006 to May 2012. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Participants With Myelofibrosis and Myelodysplastic Syndrome | 8/58 (13.8%) | 18/58 (31%) | 58/58 (100%) |
| Event | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| Secondary graft failureBlood and lymphatic system disorders | 6/58 |
| Elevated transminitisHepatobiliary disorders | 6/58 |
| Infectious pneumoniaInfections and infestations | 3/58 |
| ThrombocytopeniaBlood and lymphatic system disorders | 3/58 |
| GI GvHDGastrointestinal disorders | 2/58 |
| Veno-occlusive diseaseHepatobiliary disorders | 2/58 |
| Renal failureRenal and urinary disorders | 2/58 |
| Skin GvHDSkin and subcutaneous tissue disorders | 1/58 |
| Liver GvHDBlood and lymphatic system disorders | 1/58 |
| Hemolytic anemiaBlood and lymphatic system disorders | 1/58 |
| Event | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| NauseaGastrointestinal disorders | 51/58 |
| MucositisGastrointestinal disorders | 43/58 |
| InfectionsInfections and infestations | 34/58 |
| ATG induced feversInvestigations | 24/58 |
| Fluid overloadInvestigations | 22/58 |
| Elevated transminitisHepatobiliary disorders | 20/58 |
| Neutropenic feversInvestigations | 14/58 |
| Skin GvHDSkin and subcutaneous tissue disorders | 14/58 |
| Upper GI GvHDGastrointestinal disorders | 11/58 |
| DiarrheaGastrointestinal disorders | 11/58 |
| Age, Categorical(Participants) | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 45 |
| >=65 years | 13 |
| Age, Continuous(years) | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| Median | 59 (27 to 72) |
| Sex: Female, Male(Participants) | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| Female | 26 |
| Male | 32 |
| Race (NIH/OMB)(Participants) | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 53 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Participants With Myelofibrosis and Myelodysplastic Syndrome |
|---|---|
| United States | 58 |
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