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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-01477 | Registry Identifier | NCI CTRP |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Busulfan | Drug | Test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Non-relapse mortality at 100 days post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Uday Popat, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants With Myelofibrosis and Myelodysplastic Syndrome | Allogeneic stem cell transplantation (SCT) with preparative regimen of fludarabine and busulfan in myelofibrosis and myelodysplastic syndrome |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants With Myelofibrosis and Myelodysplastic Syndrome | Allogeneic stem cell transplantation (SCT) with preparative regimen of fludarabine and busulfan in myelofibrosis and myelodysplastic syndrome |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Count of Participants | Participants | Non-relapse mortality at 100 days post-transplant |
|
|
January 2006 to May 2012
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants With Myelofibrosis and Myelodysplastic Syndrome | Allogeneic stem cell transplantation (SCT) with preparative regimen of fludarabine and busulfan in myelofibrosis and myelodysplastic syndrome |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI GvHD | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infections | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Popat,Uday,M.D. / Stem Cell Transplantation | UT MD Anderson Cancer Center | 713-745-3055 | UPOPAT@MDANDERSON.ORG |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 9, 2012 | Nov 7, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| D013920 | Thrombocythemia, Essential |
| D011087 | Polycythemia Vera |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D002066 | Busulfan |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| C512542 | thymoglobulin |
| D000961 | Antilymphocyte Serum |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Fludarabine | Drug | 40 mg/m^2 by vein daily over 1 hour x 4 days |
|
|
| Thymoglobulin (ATG) | Drug | 2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor |
|
|
| Up to 3 years post-transplant |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | Up to 3 years post-transplant |
|
|
|
| 8 |
| 58 |
| 18 |
| 58 |
| 58 |
| 58 |
| Skin GvHD | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Infectious pneumonia | Infections and infestations | Systematic Assessment |
|
| Veno-occlusive disease | Hepatobiliary disorders | Systematic Assessment |
|
| Liver GvHD | Blood and lymphatic system disorders | Systematic Assessment |
|
| Secondary graft failure | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hemolytic anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | Systematic Assessment |
|
| Elevated transminitis | Hepatobiliary disorders | Systematic Assessment |
|
| Septic shock | Infections and infestations | Systematic Assessment |
|
| Poor graft function | Blood and lymphatic system disorders | Systematic Assessment |
|
| ABO incompatibility | Blood and lymphatic system disorders | Systematic Assessment |
|
| ATG induced fevers | Investigations | Systematic Assessment |
|
| Fluid overload | Investigations | Systematic Assessment |
|
| GI GvHD | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | Systematic Assessment |
|
| Upper GI GvHD | Gastrointestinal disorders | Systematic Assessment |
|
| Renal insufficiency | Renal and urinary disorders | Systematic Assessment |
|
| Liver GvHD | Hepatobiliary disorders | Systematic Assessment |
|
| Veno-occlusive disease | Hepatobiliary disorders | Systematic Assessment |
|
| Neutropenic fevers | Investigations | Systematic Assessment |
|
| Headaches | General disorders | Systematic Assessment |
|
| Infectious pneumonia | Infections and infestations | Systematic Assessment |
|
| ATG induced shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Skin GvHD | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hypertension | Cardiac disorders | Systematic Assessment |
|
| Ascites | Hepatobiliary disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Hemorrhagic cystits | Renal and urinary disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| BK virus associated hemorrhagic cystitis | Infections and infestations | Systematic Assessment |
|
| Elevated transminitis | Hepatobiliary disorders | Systematic Assessment |
|
| Altered mental status changes | Nervous system disorders | Systematic Assessment |
|
| Cytokine release syndrome | Investigations | Systematic Assessment |
|
| Cellulitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| ATG induced skin rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Fevers | Investigations | Systematic Assessment |
|
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| D001778 | Blood Coagulation Disorders |
| D013922 | Thrombocytosis |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
| D019046 | Bone Marrow Neoplasms |
| D019337 | Hematologic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008698 |
| Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| Title | Measurements |
|---|---|
|
| Complete hematological remission |
|