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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00237 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2056.00 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| P01CA018029 | U.S. NIH Grant/Contract | View source | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This phase II trial studies the side effects and best dose of total-body irradiation when given together with fludarabine phosphate followed by a donor peripheral stem cell transplant in treating patients with myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD). Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PRIMARY OBJECTIVES:
I. Decrease the incidence of day-200 hematopoietic cell transplantation (HCT) failure to < 20% in patients with MDS-Refractory anemia (RA)-(ringed sideroblasts [RS])/MPD and in patients with chronic myelomonocytic leukemia (CMML)/refractory anemia with excess blasts (RAEB).
SECONDARY OBJECTIVES:
I. The rate of relapse/progression in patients with MPD or MDS-RA and those with CMML or MDS-RAEB.
II. The probability of progression free survival (PFS) in patients with MPD or MDS-RA and those with CMML or MDS-RAEB.
III. The kinetics of donor engraftment.
IV. The incidence of infections.
OUTLINE: This is a dose-escalation study of total body irradiation (TBI).
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.
PERIPHERAL BLOOD STEM CELL (PBSC) TRANSPLANTATION: Patients undergo filgrastim (G-CSF)-mobilized PBSC infusion after TBI on day 0.
IMMUNOSUPPRESSION:
Matched Related Donor: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56, followed by a taper until day 180. Patients also receive mycophenolate mofetil (MMF) PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.
Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.
After completion of study treatment, patients are followed periodically.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - Dose Level 1 | Experimental | Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
| Arm A - Dose Level 2 | Experimental | Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclosporine | Drug | Given PO |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With HCT Failure. | HCT failure will be defined as graft rejection (defined as < 5% donor T-cell chimerism) or disease progression within 200 days of transplant. | 200 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Had Infections | Number of patients who experienced bacterial, fungal, or viral infections. | 1 year |
| Number of Patients Who Engrafted | Continued engraftment will be defined as the detection of donor T-cells (CD3+) as a proportion of the total T-cell of greater than 5%. |
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Inclusion Criteria:
Patients aged >= 50 and < 75 years (yrs) with CMML, or previously untreated MDS or MPD
Patients aged < 50 yrs at high risk for regimen related toxicity using standard high dose regimens; factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart or previous failed HCT
An human leukocyte antigen (HLA)-identical related or an HLA-matched unrelated donor (Fred Hutchinson Cancer Research Center [FHCRC] matching allowed will be Grade 1.0 to 2.1) is available
Recovery from the effects of previous chemotherapy, with a minimum of 21 days from initiation of last therapy; hydroxyurea or anagrelide may be used to manage elevated cell counts in patients up to the time they begin therapy under this protocol
Patients < 12 yrs of age must be discussed on a case by case basis with the primary investigator (PI) of the protocol prior to registration
A signed informed consent form or minor assent form
MDS: MDS classifiable by the World Health Organization (WHO) system as RA, RARS, refractory cytopenia with multilineage dysplasia (RCMD), RCMD and ringed sideroblasts (RCMD-RS) or RAEB
MDS: No previous myelosuppressive therapy; for the purpose of this protocol myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of inducing a complete remission (e.g., standard 7+3, high dose intermittent ARA-C [HIDAC], or Mylotarg)
MDS: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
CMML: Patients with CMML1 who have not received myelosuppressive therapy must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning; OR patients with CMML who have progressed beyond CMML1 and have received myelosuppressive chemotherapy must have < 5% marrow blasts; fewer than 5% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
MPD: Patients with polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to postpolycythemic marrow fibrosis
MPD: Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis
MPD: Chronic idiopathic myelofibrosis with peripheral blood cytopenias
MPD: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
MPD: No previous myelosuppressive therapy; for the purpose of this protocol myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of inducing a complete remission (e.g., standard 7+3, HIDAC, or Mylotarg)
Atypical chronic myeloid leukemia (CML): Philadelphia chromosome-negative patients with a diagnosis of atypical CML
Atypical CML: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
Atypical CML: No previous myelosuppressive therapy; for the purpose of this protocol myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of inducing a complete remission (e.g., standard 7+3, HIDAC, or Mylotarg)
Paroxysmal nocturnal hemoglobinuria (PNH): Patients with the non-aplastic form of PNH (cellular bone marrow) who have had a history of life-threatening complications of their disease including thrombotic events, severe hemolysis or Budd Chiari syndrome are eligible; other patients may be considered following approval at PCC and approval by the Principal investigator
Matched Related Donor: Related to the patient and is genotypically or phenotypically HLA-identical
Matched Related Donor: Donor age < 75 yrs unless cleared by institutional PI
Matched Related Donor: Capable of giving written, informed consent
Matched Related Donor: Donor must consent to PBSC mobilization with G-CSF and apheresis
Unrelated Donor: FHCRC matching allowed will be grades 1.0 to 2.1: Unrelated donors who are prospectively:
Unrelated Donor: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
HLA Matched Related Donor: G-CSF mobilized peripheral blood mononuclear cell (PBMC) only will be permitted as a hematopoietic stem cell (HSC) source on this protocol
HLA Matched Unrelated Donor: Donor must consent to PBSC mobilization with G-CSF and apheresis; bone marrow unrelated donors are not eligible for this protocol
Exclusion Criteria:
Organ dysfunction as defined by the following:
Bone marrow documenting blast count >= 10% or >= 5% in CMML patients who have progressed beyond CMML1 and received myelosuppressive chemotherapy
Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
Presence of >= 5% circulating leukemic blasts (in the peripheral blood) detected by standard pathology
Active central nervous system (CNS) involvement of disease
Karnofsky performance score < 70% or Lansky-Play Performance score < 70 for pediatric patients
Life expectancy severely limited by diseases other than malignancy
Fungal infections with radiological progression after receipt of amphotericin product or active triazole for > 1 month
Active bacterial infection
Patients of fertile age who refuse contraception for a twelve month period post-transplant
Females who are pregnant or breastfeeding
Human immunodeficiency virus (HIV) seropositivity
Severe psychological illness such as major psychosis (e.g. schizophrenia), major bipolar depression, or suicidal situational depression
Matched Related Donor: Identical twin
Matched Related Donor: Any contra-indication to the administration of subcutaneous G-CSF at a dose of 16mg/kg/d for five consecutive days
Matched Related Donor: Serious medical or psychological illness
Matched Related Donor: Pregnant or lactating females
Matched Related Donor: Prior malignancy within the preceding five yrs, with the exception of non-melanoma skin cancers
Matched Related Donor: HIV seropositivity
Unrelated Donor: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results
Unrelated Donor: Marrow donors
Unrelated Donor: Donors who are HIV-positive and/or medical conditions that would result in increased risk to the donor G-CSF mobilization and G-PBMC collections
Unrelated Donor: Serious medical or psychological illness
Unrelated Donor: Pregnant or lactating females
Unrelated Donor: Prior malignancy within the preceding five yrs, with the exception of non-melanoma skin cancers
Unrelated Donor: HIV seropositivity
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| Name | Affiliation | Role |
|---|---|---|
| Brenda Sandmaier | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LDS Hospital | Salt Lake City | Utah | 84143 | United States | ||
| Veterans Administration Center-Seattle |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32499241 | Derived | Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187. | |
| 30630975 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A - Dose Level 1 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 3, 2016 |
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| Arm A - Dose Level 3 | Experimental | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
| Arm B - Dose Level 1 | Experimental | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
| Arm B - Dose Level 2 | Experimental | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
| Arm B - Dose Level 3 | Experimental | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
|
| Fludarabine Phosphate | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Mycophenolate Mofetil | Drug | Given PO |
|
|
| Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo transplantation |
|
|
| Peripheral Blood Stem Cell Transplantation | Procedure | Undergo PBSC transplant |
|
|
| Total-Body Irradiation | Radiation | Undergo TBI |
|
|
| 1 year |
| Number of Patients With Progression-free Survival | Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia. | 1 year |
| Number of Patients With Relapse/Progression | Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia. | 1 year |
| Seattle |
| Washington |
| 98108 |
| United States |
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| Derived |
| Monaco F, Scott BL, Chauncey TR, Petersen FB, Storer BE, Baron F, Flowers ME, Deeg HJ, Maloney DG, Storb R, Sandmaier BM. Total body irradiation dose escalation decreases risk of progression and graft rejection after hematopoietic cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms. Haematologica. 2019 Jun;104(6):1221-1229. doi: 10.3324/haematol.2018.199398. Epub 2019 Jan 10. |
| FG001 | Arm A - Dose Level 2 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| FG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| FG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| FG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| FG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| COMPLETED |
|
| NOT COMPLETED |
|
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm A - Dose Level 1 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| BG001 | Arm A - Dose Level 2 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| BG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| BG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| BG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| BG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| BG006 | Total | Total of all reporting groups |
| 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 | Participants |
| ||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | 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 | Number of Patients With HCT Failure. | HCT failure will be defined as graft rejection (defined as < 5% donor T-cell chimerism) or disease progression within 200 days of transplant. | No patients were enrolled on arms A2 and A3 because dose escalation was never triggered. | Posted | Count of Participants | Participants | 200 days |
|
|
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients Who Had Infections | Number of patients who experienced bacterial, fungal, or viral infections. | No patients were enrolled on arms A2 and A3 because dose escalation was never triggered. | Posted | Count of Participants | Participants | 1 year |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients Who Engrafted | Continued engraftment will be defined as the detection of donor T-cells (CD3+) as a proportion of the total T-cell of greater than 5%. | No patients were enrolled on arms A2 and A3 because dose escalation was never triggered. | Posted | Count of Participants | Participants | 1 year |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Progression-free Survival | Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia. | No patients were enrolled on arms A2 and A3 because dose escalation was never triggered. | Posted | Count of Participants | Participants | 1 year |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Relapse/Progression | Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia. | No patients were enrolled on arms A2 and A3 because dose escalation was never triggered. | Posted | Count of Participants | Participants | 1 year |
|
AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.
No patients were enrolled on arms A2 and A3 because dose escalation was never triggered.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A - Dose Level 1 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. | 10 | 36 | 3 | 36 | 16 | 36 |
| EG001 | Arm A - Dose Level 2 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. | 10 | 12 | 7 | 12 | 9 | 12 |
| EG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. | 3 | 5 | 2 | 5 | 2 | 5 |
| EG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. | 9 | 24 | 4 | 24 | 13 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| GVHD | Immune system disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Mucosal infection | Infections and infestations | Systematic Assessment |
| ||
| Multi-organ failure | General disorders | Systematic Assessment |
| ||
| Psychiatric disorders - Other, specify (altered mental status) | Psychiatric disorders | Systematic Assessment |
| ||
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
| ||
| Suicide attempt | Psychiatric disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| ||
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Ascites | Gastrointestinal disorders | Systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Atrial flutter | Cardiac disorders | Systematic Assessment |
| ||
| Blood antidiuretic hormone abnormal | Investigations | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Carbon monoxide diffusing capacity decreased | Investigations | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Flu like symptoms | General disorders | Systematic Assessment |
| ||
| Gastric hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastritis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Heart failure | Cardiac disorders | Systematic Assessment |
| ||
| Hemolysis | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Hemolytic uremic syndrome | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment |
| ||
| Myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Pericardial effusion | Cardiac disorders | Systematic Assessment |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Syncope | Nervous system disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Brenda M. Sandmaier | Fred Hutchinson Cancer Research Center | (206) 667-4961 | bsandmai@fredhutch.org |
| Aug 6, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D054438 | Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D013920 | Thrombocythemia, Essential |
| D009196 | Myeloproliferative Disorders |
| D006457 | Hemoglobinuria, Paroxysmal |
| D011087 | Polycythemia Vera |
| D055728 | Primary Myelofibrosis |
| D000753 | Anemia, Refractory |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| 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 |
| D001778 | Blood Coagulation Disorders |
| D013922 | Thrombocytosis |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
| D019046 | Bone Marrow Neoplasms |
| D019337 | Hematologic Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D003524 | Cyclosporins |
| C042382 | fludarabine phosphate |
| D009173 | Mycophenolic Acid |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| 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 |
| D011878 | Radiotherapy |
| D008919 | Investigative Techniques |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
|
| OG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
|
Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
|
|
Arm A - patients with MPD or MDS-RA/RARS Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG002 | Arm A - Dose Level 3 | Arm A - patients with MPD or MDS-RA/RARS Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG003 | Arm B - Dose Level 1 | Arm B - patients with MDS-RAEB or CMML Dose Level 1 - 300 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG004 | Arm B - Dose Level 2 | Arm B - patients with MDS-RAEB or CMML Dose Level 2 - 400 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
| OG005 | Arm B - Dose Level 3 | Arm B - patients with MDS-RAEB or CMML Dose Level 3 - 450 cGy TBI NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. PBSC TRANSPLANTATION: Patients undergo filgrastim-mobilized PBSC infusion after TBI on day 0. IMMUNOSUPPRESSION: Matched Related Donor: Patients receive cyclosporine PO BID on days -3 to 56, followed by a taper until day 180. Patients also receive MMF PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27. Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96. |
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