Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus, and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00358657
• Collaborator: National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 14
• Locations: 3
• Arm: 1
• Actual Duration (Months): 156
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects of fludarabine phosphate, cyclophosphamide and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus in treating patients with primary immunodeficiency disorders or noncancerous inherited disorders. Giving low doses of chemotherapy and total-body irradiation before a bone marrow transplant helps prepare the patient's body to accept the incoming donor's bone marrow and decrease the risk that the patient's immune system will reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus after the transplant may help decrease this from happening.

Condition or Disease	Intervention/Treatment	Phase
Immunodeficiency Syndrome; Severe Aplastic Anemia; Genetic Disorder	Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Sirolimus; Drug: Tacrolimus; Radiation: Total-Body Irradiation	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. Determine safety of nonmyeloablative conditioning and hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA)-haploidentical related donors for patients with nonmalignant inherited disorders who do not have an HLA-matched related or unrelated donor.

SECONDARY OBJECTIVES:

1. Determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical related donor graft can establish mixed chimerism (> 5% cluster of differentiation [CD]3+ donor T-cell chimerism) in patients with nonmalignant inherited disorders.

2. Transplant related mortality at day 100.

3. Incidence and severity of graft-versus-host disease (GHVD).

4. Immune reconstitution.

5. Infections during the first 200 days after HCT.

OUTLINE:

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6 and -5; and undergo total body irradiation on day -1.

TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on days 3 and 4, and mycophenolate mofetil orally (PO) every 8 hours on days 5-30 then twice daily (BID) to day 40, and then if there is no evidence of active GVHD and donor engraftment is > 95% (or by principal investigator [PI] approval) taper until approximately day 96, or faster at discretion of PI. Patients also receive tacrolimus IV continuously over 22-24 hours starting on day 5 post-transplant and continue on tacrolimus through day 100 followed by a taper to approximately day 180 if there is no evidence of GVHD and their graft is doing well. Patients may convert to oral tacrolimus given BID or three times daily (TID) when the patient is able to take medications orally and has a therapeutic drug level. In addition, patients will receive sirolimus PO beginning on day 5 through day 180 followed by a taper to approximately day 210 if there is no evidence of GVHD and their graft is doing well.

After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months, and then annually for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: HLA-Haploidentical Related Marrow Grafts for the Treatment of Primary Immunodeficiencies and Other Nonmalignant Disorders Using Conditioning With Low-Dose Cyclophosphamide, TBI and Fludarabine and Postgrafting Cyclophosphamide
• Actual Study Start Date: May 24, 2006
• Actual Primary Completion Date: Aug 17, 2018
• Actual Study Completion Date: May 25, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemo, total-body irradiation, transplant) See Detailed Description

Procedure: Allogeneic Bone Marrow Transplantation; Undergo allogeneic bone marrow transplantation; Other Names: Allo BMT Allogeneic BMT ; Drug: Cyclophosphamide; Given IV; Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Drug: Fludarabine Phosphate; Given IV; Other Names: 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Mycophenolate Mofetil; Given PO; Other Names: Cellcept MMF ; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic bone marrow transplantation; Other Names: Non-myeloablative allogeneic transplant Nonmyeloablative Stem Cell Transplantation NST ; Drug: Sirolimus; Given PO; Other Names: AY 22989 RAPA Rapamune Rapamycin SILA 9268A WY-090217 ; Drug: Tacrolimus; Given IV or PO; Other Names: FK 506 Fujimycin Hecoria Prograf Protopic ; Radiation: Total-Body Irradiation; Undergo total-body irradiation; Other Names: TOTAL BODY IRRADIATION Whole-Body Irradiation

Outcome Measures

Primary Outcome Measures

1. Graft Rejection [Day 84]

   Number of patients with graft rejection (CD3 donor chimerisms <5%).

2. Graft Failure [Day 84]

   Number of patients with graft failure (grade IV thrombocytopenia and neutropenia after day 21 that lasts > 2 weeks andn is refractory to growth factor support).

Secondary Outcome Measures

1. Proportion of Patients Who Achieve Greater Than 5% Donor T-cell Chimerism [By day 84]

   Number of patients who achieve greater than 5% donor T-cell (CD3+) chimerisms

2. Number of Patients With Transplant Related Mortality [Day 100 post transplant]

   The number of patients with transplant related mortality

3. Incidence of Grade I/II Acute Graft Versus Host Disease (GVHD) [Day 100 post transplant]

   Number of patients diagnosed with overall GI/G2 acute GVHD by Day 100

4. Incidence of Grade III/IV Acute Graft Versus Host Disease (GVHD) [Day 100 post transplant]

   Number of patients diagnosed with overall GIII/IV acute GVHD by Day 100

5. Incidence of Chronic GVHD [1 year post transplant]

   Number of patients diagnosed with chronic GVHD by 1 year post transplant

6. Immune Reconstitution [1 year post transplant]

   Number of patients with normal range CD3 @ 1 year post transplant

7. Number of Patients With Infections [Through day 200 after HCT]

   Number of patients with clinically significant infections requiring treatment within 200 days after HCT

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary immunodeficiency disorder or other nonmalignant inherited disease (except Fanconi anemia) treatable by allogeneic HCT

• Patients with pre-existing medical conditions or other factors that renders them at high risk for regimen related toxicity or ineligible for conventional myeloablative HCT and who do not have HLA-matched related or unrelated donors

• Patients with a related donor who is identical for one HLA haplotype

• Acquired aplastic anemia: severe aplastic anemia (SAA) is defined as follows:

• Bone marrow cellularity < 25%, or marrow cellularity < 50% but with < 30% residual hematopoietic cells

• Two out of three of the following (in peripheral blood): neutrophils < 0.5 x 10^{9/L; platelets < 20 x 10}9/L; reticulocytes < 20 x 10^9/L

• SAA diagnostic criteria may be applied to assessment at initial diagnosis or follow-up assessments

• DONOR: Related donors who are identical for one HLA haplotype

• DONOR: Bone marrow will be the only allowed stem cell source

Exclusion Criteria:

• Fanconi anemia

• Suitably HLA-matched related or unrelated donors

• Patients with metabolic storage diseases who have severe central nervous system (CNS) involvement of disease, defined as intelligence quotient (IQ) score < 70

• Cardiac ejection fraction < 30% (or, if unable to obtain ejection fraction, shortening fraction < 26%) on multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (echo), symptomatic coronary artery disease, or other cardiac failure requiring therapy; patients with a history of, or current cardiac disease should be evaluated with appropriate cardiac studies and/or cardiology consult; patients with a shortening fraction of < 26% must be seen by cardiology for approval

• Poorly controlled hypertension despite anti-hypertensive medications

• Patients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary disease

• Positive for human immunodeficiency virus (HIV)

• Females who are pregnant (beta-human chorionic gonadotropin positive [beta-HCG+]) or breast-feeding

• Fertile men or women who are unwilling to use contraceptives during HCT and up to 12 months post-treatment

• Patients with fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month will not be eligible for this protocol (either regimen A or B)

• DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the host-versus-graft (HVG) direction; patients are homozygous and donor is heterozygous

• DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight)

• DONOR: HIV-positive donors

• DONOR: A positive anti-donor cytotoxic cross match is absolute donor exclusion

• DONOR: < 6 months old and > 75 years old

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital at TriStar Centennial	Nashville	Tennessee	United States	37203
2	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
3	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Kanwaldeep Mallhi, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 22, 2020

More Information

Publications

None provided.

• Responsible Party: Kanwaldeep K Mallhi, Assistant Professor, Clinical Research Division, Fred Hutch, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00358657
• Other Study ID Numbers: 2032.00; NCI-2010-00192; 2032; 2032.00; P01HL122173; P30CA015704; RG9213024
• First Posted: Aug 1, 2006
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Anemia, Aplastic; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Disease; Mycophenolic Acid; Sirolimus; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Period Title: Overall Study
STARTED	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Overall Participants	14
Age (Count of Participants)
<=18 years	13 92.9%
Between 18 and 65 years	1 7.1%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	10.7
Sex: Female, Male (Count of Participants)
Female	4 28.6%
Male	10 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	14 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 7.1%
Asian	3 21.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 50%
White	3 21.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%

Outcome Measures

1. Primary Outcome

Title	Graft Rejection
Description	Number of patients with graft rejection (CD3 donor chimerisms <5%).
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	1 7.1%

2. Primary Outcome

Title	Graft Failure
Description	Number of patients with graft failure (grade IV thrombocytopenia and neutropenia after day 21 that lasts > 2 weeks andn is refractory to growth factor support).
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Proportion of Patients Who Achieve Greater Than 5% Donor T-cell Chimerism
Description	Number of patients who achieve greater than 5% donor T-cell (CD3+) chimerisms
Time Frame	By day 84

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	13 92.9%

4. Secondary Outcome

Title	Number of Patients With Transplant Related Mortality
Description	The number of patients with transplant related mortality
Time Frame	Day 100 post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Incidence of Grade I/II Acute Graft Versus Host Disease (GVHD)
Description	Number of patients diagnosed with overall GI/G2 acute GVHD by Day 100
Time Frame	Day 100 post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	7 50%

6. Secondary Outcome

Title	Incidence of Grade III/IV Acute Graft Versus Host Disease (GVHD)
Description	Number of patients diagnosed with overall GIII/IV acute GVHD by Day 100
Time Frame	Day 100 post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	5 35.7%

7. Secondary Outcome

Title	Incidence of Chronic GVHD
Description	Number of patients diagnosed with chronic GVHD by 1 year post transplant
Time Frame	1 year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	11 78.6%

8. Secondary Outcome

Title	Immune Reconstitution
Description	Number of patients with normal range CD3 @ 1 year post transplant
Time Frame	1 year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	13
Count of Participants [Participants]	4 28.6%

9. Secondary Outcome

Title	Number of Patients With Infections
Description	Number of patients with clinically significant infections requiring treatment within 200 days after HCT
Time Frame	Through day 200 after HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
Measure Participants	14
Count of Participants [Participants]	11 78.6%

Adverse Events

Time Frame	Day 200 post initiation of conditioning therapy
Arm/Group Title	Treatment (Chemo, Total-body Irradiation, Transplant)
Arm/Group Description	See Detailed Description Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplantation Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic bone marrow transplantation Sirolimus: Given PO Tacrolimus: Given IV or PO Total-Body Irradiation: Undergo total-body irradiation
All Cause Mortality
	Treatment (Chemo, Total-body Irradiation, Transplant)
	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)
Serious Adverse Events
	Treatment (Chemo, Total-body Irradiation, Transplant)
	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)
Gastrointestinal disorders
Pancreatitis with shock	1/14 (7.1%)	1
Infections and infestations
Sepsis	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia requiring mechanical ventilation	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Chemo, Total-body Irradiation, Transplant)
	Affected / at Risk (%)	# Events
Total	8/14 (57.1%)
Blood and lymphatic system disorders
Febrile neutropenia	3/14 (21.4%)	3
Hemolytic uremic syndrome	1/14 (7.1%)	1
Cardiac disorders
Pericardial effusion	1/14 (7.1%)	1
Gastrointestinal disorders
Typhlitis	1/14 (7.1%)	1
Pancreatisis	1/14 (7.1%)	1
Mucositis oral	1/14 (7.1%)	1
Investigations
Blood bilirubin increased	1/14 (7.1%)	1
Nervous system disorders
Seizure	1/14 (7.1%)	1
Renal and urinary disorders
Acute kidney injury	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/14 (7.1%)	1
Vascular disorders
Hypotension	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.