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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-01785 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 1913.00 | Other Identifier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| P30CA015704 | U.S. NIH Grant/Contract | View source | |
| P01HL036444 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| National Cancer Institute (NCI) | NIH |
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This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.
PRIMARY OBJECTIVE:
I. Determine the incidence and severity of acute graft-versus-host disease (GvHD).
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy.
II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics.
III. Determine the incidence of donor engraftment.
IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3.
V. Determine the incidence and severity of chronic GvHD.
VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr).
VII. Determine the incidence of relapse.
VIII. Determine relapse-free survival.
IX. Determine the incidence of Epstein-Barr virus (EBV) activation.
OUTLINE:
Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.
After completion of study treatment, patients are followed at 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, PBSC transplant) | Experimental | Patients receive fludarabine phosphate IV over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic PBSC transplant on day 0. Patients then receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fludarabine phosphate | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of acute GvHD | Maximum grade of acute GVHD and the number of therapies required to treat GVHD will be determined. | Day 100 post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy | At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3 | |
| Thymoglobulin pharmacokinetics | On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900 |
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Inclusion Criteria:
Exclusion Criteria:
Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal
Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
Impaired renal function (creatinine > 2 times normal or estimated creatinine clearance < 60 ml/min)
Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or acceleration of HIV replication
Female patients who are pregnant or breast feeding
Life expectancy severely limited by diseases other than malignancy
DONOR: donors who for any reason are unable to tolerate the mobilization and leukapheresis procedure
DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive
DONOR: female donors who have a positive pregnancy test
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| Name | Affiliation | Role |
|---|---|---|
| H. Joachim Deeg | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| busulfan | Drug | Given IV |
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| anti-thymocyte globulin | Biological | Given IV |
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| tacrolimus | Drug | Given IV and orally |
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| methotrexate | Drug | Given IV |
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| peripheral blood stem cell transplantation | Procedure | Undergo allogeneic PBSC transplant |
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| allogeneic hematopoietic stem cell transplantation | Procedure | Undergo allogeneic PBSC transplant |
|
| laboratory biomarker analysis | Other | Correlative studies |
|
| Incidence of donor cell engraftment | By day 100 |
| Incidence of system toxicities >= grade 3 as graded per CTCAE v.3 | Up to day 100 after transplantation |
| Incidence of chronic GvHD | Day 100 |
| Incidence of non-relapse mortality defined as death without history of post-transplant relapse | At day 100 |
| Incidence of non-relapse mortality defined as death without history of post-transplant relapse | At 1 year |
| Incidence of relapse | Defined by either morphological or cytogenetic evidence of chronic myelogenous leukemia (CML), AML, MDS or other myeloproliferative disease in marrow, blood, or other sites, or laboratory evidence of residual disease. | At 1 year |
| Relapse-free survival | At 1 year |
| Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR) | Up to 1 year |
| ID | Term |
|---|---|
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D000013 | Congenital Abnormalities |
| D001752 | Blast Crisis |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D019337 | Hematologic Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C042382 | fludarabine phosphate |
| D002066 | Busulfan |
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| D016559 | Tacrolimus |
| D008727 | Methotrexate |
| C015342 | merphos |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| 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 |
| D018942 | Macrolides |
| D007783 | Lactones |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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