Trial Outcomes & Findings for Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia (NCT NCT00453388)

Results Overview

Number of subjects who engrafted. Engraftment defined as greater than 95% donor chimerism.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Up to Day 200

Results posted on

2020-01-29

Participant Flow

Participant milestones

Participant milestones
Measure	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Overall Study STARTED	5	1
Overall Study COMPLETED	5	1
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 Participants Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 Participants Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	—	5 Participants n=7 Participants	1 Participants n=5 Participants	—	6 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	—	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Age, Categorical >=65 years	—	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Age, Continuous	—	11.1 years n=7 Participants	11.9 years n=5 Participants	—	11.1 years n=21 Participants
Sex: Female, Male Female	—	5 Participants n=7 Participants	0 Participants n=5 Participants	—	5 Participants n=21 Participants
Sex: Female, Male Male	—	0 Participants n=7 Participants	1 Participants n=5 Participants	—	1 Participants n=21 Participants
Region of Enrollment United States	—	3 participants n=7 Participants	1 participants n=5 Participants	—	4 participants n=21 Participants
Region of Enrollment Brazil	—	2 participants n=7 Participants	0 participants n=5 Participants	—	2 participants n=21 Participants

PRIMARY outcome

Timeframe: Up to Day 200

Population: No subjects meeting the criteria for Arms I or IV were enrolled.

Number of subjects who engrafted. Engraftment defined as greater than 95% donor chimerism.

Outcome measures

Outcome measures
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 Participants Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 Participants Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Number of Patients Who Engraft at Each Dose of TBI Used	—	5 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 100

Population: No subjects meeting the criteria for Arms I or IV were enrolled.

Number of subjects who developed maximum grade acute graft-vs-host disease aGVHD Stages Skin: 1. \- a maculopapular eruption involving \< 25% BSA 2. \- a maculopapular eruption involving 25 - 50% BSA 3. \- generalized erythroderma 4. \- generalized erythroderma with bullous formation and often with desquamation Liver: 1. \- bilirubin 2.0 - 3.0 mg/100 mL 2. \- bilirubin 3 - 5.9 mg/100 mL 3. \- bilirubin 6 - 14.9 mg/100 mL 4. \- bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Outcome measures

Outcome measures
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 Participants Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 Participants Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Incidence of Grades III-IV Acute GVHD	—	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to Day 200

Population: No subjects meeting the criteria for Arms I or IV were enrolled.

Number of subjects who expired due to transplant-related mortality

Outcome measures

Outcome measures
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 Participants Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 Participants Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Incidence of Transplant-related Mortality	—	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to Day 100

Population: No subjects meeting the criteria for Arms I or IV were enrolled.

Number of subjects who developed reportable AEs, assessed using adapted version of the Common Toxicity Criteria

Outcome measures

Outcome measures
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 Participants Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 Participants Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Incidence of Adverse Events	—	3 Participants	0 Participants	—

Adverse Events

Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 participants at risk Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 participants at risk Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Infections and infestations Death	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	20.0% 1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.
Gastrointestinal disorders severe abdominal pain associated with GVHD	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	20.0% 1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.

Other adverse events

Other adverse events
Measure	Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) n=5 participants at risk Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) n=1 participants at risk Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI	Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
Respiratory, thoracic and mediastinal disorders pulmonary hemorrage	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	20.0% 1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.
Respiratory, thoracic and mediastinal disorders acute respiratory distress syndrome	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	20.0% 1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.
Gastrointestinal disorders diarrhea	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	20.0% 1/5 • Number of events 1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.
Gastrointestinal disorders Mucositis	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	40.0% 2/5 • Number of events 2 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.
Hepatobiliary disorders elevated bilitrubin	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	40.0% 2/5 • Number of events 3 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	0.00% 0/1 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.	— 0/0 • AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200 No subjects meeting the criteria for Arms I or IV were enrolled.

Additional Information

Dr. Hans-Peter Kiem

Fred Hutchinson Cancer Research Center

Phone: 206-667-4425

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place