Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00553098
• Collaborator: National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 29
• Locations: 6
• Arm: 1
• Patients Per Site: 4.8

Study Details

Study Description

Brief Summary

This phase II trial studies fludarabine phosphate and total-body irradiation with or without alemtuzumab followed by donor stem cell transplant to see how well it works in treating patients with immunodeficiency or other nonmalignant inherited disorders. Giving chemotherapy, such as fludarabine phosphate, a monoclonal antibody such as alemtuzumab, and radiation therapy before a donor stem cell transplant helps stop the growth of abnormal cells. It may also stop 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 abnormal cells.

Condition or Disease	Intervention/Treatment	Phase
Immunodeficiency Syndrome; Non-Cancer Diagnosis	Biological: Alemtuzumab; Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Improve donor chimerism levels in patients with inherited nonmalignant disorders undergoing hematopoietic cell transplantation (HCT) using a reduced intensity conditioning regimen either through the addition of Campath (alemtuzumab) or a slightly higher dose of total-body irradiation (TBI).

SECONDARY OBJECTIVES:

1. Decrease the incidence and severity of acute and chronic graft-versus-host disease (GVHD) through use of marrow as the stem cell source and Campath.

2. Assess disease response following HCT.

3. Immune reconstitution following HCT.

4. Incidence of infections.

5. Overall survival.

6. Percent of patients with cluster of differentiation (CD)33/CD19 donor chimerism > 50%.

OUTLINE:

CONDITIONING REGIMEN: Patients with no life-threatening viral or fungal infections within 1 month before the planned hematopoietic cell transplantation (HCT) receive alemtuzumab intravenously (IV) over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with hemophagocytic lymphohistiocytosis (HLH), immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0.

HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine IV or orally (PO) 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96.

After completion of HCT, patients are followed up at day 84, at 6, 12, 18 and 24 months post-transplantation, and then once a year for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hematopoietic Cell Transplantation for Treatment of Patients With Primary Immunodeficiencies and Other Nonmalignant Inherited Disorders Using Low-Dose TBI and Fludarabine With or Without Campath®
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemotherapy, low dose radiation) CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96.

Biological: Alemtuzumab; Given IV; Other Names: Anti-CD52 Monoclonal Antibody Campath Campath-1H LDP-03 MabCampath Monoclonal Antibody Campath-1H ; Procedure: Allogeneic Bone Marrow Transplantation; Undergo HCT; Other Names: Allo BMT Allogeneic BMT ; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo HCT; Other Names: allogeneic stem cell transplantation HSC HSCT ; Drug: Cyclosporine; Given PO or IV; Other Names: 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Neoral OL 27-400 Sandimmun Sandimmune SangCya ; 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 Oforta SH T 586 ; Other: Laboratory Biomarker Analysis; Correlative study; Drug: Mycophenolate Mofetil; Given PO or IV; Other Names: Cellcept MMF ; Radiation: Total-Body Irradiation; Undergo low dose TBI; Other Names: TOTAL BODY IRRADIATION Whole-Body Irradiation

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism [At 1 year post transplant]

   The study will be considered a success and the protocol worthy of further study if there is sufficient evidence that this rate is greater than the 50% rate observed in the most recently transplanted patients with nonmalignant disorders. Analyses will be carried out separately for the alemtuzumab recipients and the TBI recipients. We will be 80% confidence of success if a one-sided 80% confidence interval for the proportion of patients with successful chimerism exceeds 50%. Cumulative incidence will be used to evaluate the probability of chimerism.

Secondary Outcome Measures

1. Overall Survival [1 year]

   Number of patients alive at 1 year

2. Immune Reconstitution by 1 Year Post Transplant [1 year]

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

3. Disease Response by 1 Year Post Transplant [1 year]

   Number of patients at 1 year with disease response (defined as no clinical evidence of active disease and/or sufficient level of donor chimerisms to prevent disease recurrence)

4. Greater Than 50% CD33+ Donor Chimerisms at 1 Year Post Transplant [1 year]

   Number of patients who achieve greater than 50% CD33+ donor chimerisms at 1 year post transplant.

5. Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant [1 year]

   Number of Patients Who Achieve Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant

6. Clinical Significant Infection, Requiring Treatment, Within 100 Days Post Transplant [100 days]

   Number of patients who experienced a clinical significant infection, requiring treatment, within 100 days post transplant.

7. Number of Patients Diagnosed With Acute GVHD [Day 100]

   Number of patients diagnosed with acute GVHD by Day 100 post transplant

8. Number of Patients Diagnosed With Overall Grade 1 or Grade 2 Acute GVHD [Day 100]

   Number of patients diagnosed with overall grade I or grade II acute GVHD by Day 100 post transplant

9. Number of Patients Diagnosed With Overall Grade III or Grade IV Acute GVHD [Day 100]

   Number of patients diagnosed with overall Grade III or Grade IV Acute GVHD by Day 100 post transplant

10. Number of Patients Diagnosed With Chronic GVHD [1 year]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 54 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary immunodeficiency disorder or other nonmalignant inherited disease (except aplastic anemia and 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 a conventional myeloablative HCT

• Donors: Related donor who is human leukocyte antigen (HLA) genotypically identical at least at one haplotype and may be genotypically or phenotypically identical for serological typing for HLA-A, B, -C, and at the allele level for -DRB1 and -DQB1; related donors must be a match or a single allele mismatch at HLA-A, B, and C (at highest resolution available at the time of donor selection) and matched at DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing

• Donors: Unrelated donors who are prospectively:

• Matched for HLA-A, B, C, DRB1 and DQB1 by DNA typing at the highest resolution routinely available at the time of donor selection

• Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing (no mismatching for DRB1 or DQB1 is allowed)

Exclusion Criteria:

• Patients with Aplastic anemia and Fanconi anemia

• 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 of < 26%) on multi-gated acquisition (MUGA) scan or cardiac echo, symptomatic coronary artery disease, 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 < 26% may be enrolled if approved by a cardiologist

• 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 > 3mg/dl, or symptomatic biliary disease (Patients will be allowed on to the protocol with liver problems if gastroenterology approves the patient for HCT)

• Patients who are positive for human immunodeficiency virus (HIV)

• Females who are pregnant 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)

• Donors: Identical twin

• Donors: Pregnancy

• Donors: HIV positive

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

• Donors: If a patient is homozygous at a particular loci, mismatching at that loci is not allowed due to an isolated graft rejection vector, i.e., patient A0101 and the donor is A0101, A0201; such a mismatch may increase the risk of graft rejection; if patient and donor pairs are both homozygous at a mismatched loci, they are considered a two-HLA antigen mismatch, i.e., the patient is A0101 and the donor is A*0201, and this type of mismatch is not allowed

• Donor: Donor < 6 months old, > 75 years old

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
2	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
3	Oregon Health and Science University	Portland	Oregon	United States	97239
4	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
5	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
6	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53201

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Lauri Burroughs, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lauri Burroughs, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00553098
• Other Study ID Numbers: 2007.00; NCI-2009-01550; 2007; 2007.00; P30CA015704
• First Posted: Nov 4, 2007
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Immunologic Deficiency Syndromes; Cyclosporine; Mycophenolic Acid; Antineoplastic Agents, Immunological; Alemtuzumab; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Period Title: Overall Study
STARTED	29
COMPLETED	28
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Overall Participants	28
Age (Count of Participants)
<=18 years	24 85.7%
Between 18 and 65 years	4 14.3%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	12 42.9%
Male	16 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%
Not Hispanic or Latino	27 96.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 3.6%
Black or African American	1 3.6%
White	22 78.6%
More than one race	4 14.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism
Description	The study will be considered a success and the protocol worthy of further study if there is sufficient evidence that this rate is greater than the 50% rate observed in the most recently transplanted patients with nonmalignant disorders. Analyses will be carried out separately for the alemtuzumab recipients and the TBI recipients. We will be 80% confidence of success if a one-sided 80% confidence interval for the proportion of patients with successful chimerism exceeds 50%. Cumulative incidence will be used to evaluate the probability of chimerism.
Time Frame	At 1 year post transplant

Outcome Measure Data

Analysis Population Description

Excludes 9 patients who expired prior to 1 year

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	19
Count of Participants [Participants]	13 46.4%

2. Secondary Outcome

Title	Overall Survival
Description	Number of patients alive at 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Excludes 3 patients with graft rejection and second transplant prior to 1 year.

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	25
Count of Participants [Participants]	19 67.9%

3. Secondary Outcome

Title	Immune Reconstitution by 1 Year Post Transplant
Description	Number of patients with normal range CD3 at 1 year post transplant
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Excludes 16 patients: 13 patients who did not achieve 1 year time point (9 expired, 4 went to second transplant) and 3 patients for whom no data was sent at 1 year from external site

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoietic S
Measure Participants	12
Count of Participants [Participants]	7 25%

4. Secondary Outcome

Title	Disease Response by 1 Year Post Transplant
Description	Number of patients at 1 year with disease response (defined as no clinical evidence of active disease and/or sufficient level of donor chimerisms to prevent disease recurrence)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Excludes 9 patients who expired prior to 1 year time point.

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoietic S
Measure Participants	19
Count of Participants [Participants]	15 53.6%

5. Secondary Outcome

Title	Greater Than 50% CD33+ Donor Chimerisms at 1 Year Post Transplant
Description	Number of patients who achieve greater than 50% CD33+ donor chimerisms at 1 year post transplant.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Excludes 9 patients who expired prior to 1 year time point

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	19
Count of Participants [Participants]	8 28.6%

6. Secondary Outcome

Title	Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant
Description	Number of Patients Who Achieve Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Excludes 9 patients who expired prior to 1 year time point

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoietic
Measure Participants	19
Count of Participants [Participants]	16 57.1%

7. Secondary Outcome

Title	Clinical Significant Infection, Requiring Treatment, Within 100 Days Post Transplant
Description	Number of patients who experienced a clinical significant infection, requiring treatment, within 100 days post transplant.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoietic Ste
Measure Participants	28
Count of Participants [Participants]	21 75%

8. Secondary Outcome

Title	Number of Patients Diagnosed With Acute GVHD
Description	Number of patients diagnosed with acute GVHD by Day 100 post transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	28
Count of Participants [Participants]	18 64.3%

9. Secondary Outcome

Title	Number of Patients Diagnosed With Overall Grade 1 or Grade 2 Acute GVHD
Description	Number of patients diagnosed with overall grade I or grade II acute GVHD by Day 100 post transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

Excludes 10 patients who were not diagnosed with acute GVHD

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	18
Count of Participants [Participants]	12 42.9%

10. Secondary Outcome

Title	Number of Patients Diagnosed With Overall Grade III or Grade IV Acute GVHD
Description	Number of patients diagnosed with overall Grade III or Grade IV Acute GVHD by Day 100 post transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

Excludes 10 patients who were not diagnosed with acute GVHD

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	18
Count of Participants [Participants]	6 21.4%

11. Secondary Outcome

Title	Number of Patients Diagnosed With Chronic GVHD
Description	Number of patients diagnosed with chronic GVHD within 1 year post transplant
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Excludes 6 patients who expired prior to Day 100

Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
Measure Participants	22
Count of Participants [Participants]	8 28.6%

Adverse Events

Time Frame	Day 200 post initiation of conditioning therapy
Arm/Group Title	Treatment (Chemotherapy, Low Dose Radiation)
Arm/Group Description	CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet
All Cause Mortality
	Treatment (Chemotherapy, Low Dose Radiation)
	Affected / at Risk (%)	# Events
Total	9/28 (32.1%)
Serious Adverse Events
	Treatment (Chemotherapy, Low Dose Radiation)
	Affected / at Risk (%)	# Events
Total	10/28 (35.7%)
Cardiac disorders
Pericardial Effusion	1/28 (3.6%)	1
Cardiorspiratory Failure	3/28 (10.7%)	3
Hepatobiliary disorders
Hyperbilirubinemia	1/28 (3.6%)	1
Infections and infestations
Sepsis	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/28 (3.6%)	1
Acute Respiratory Distress Syndrome	2/28 (7.1%)	2
Pulmonary Edema	2/28 (7.1%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Low Dose Radiation)
	Affected / at Risk (%)	# Events
Total	13/28 (46.4%)
Blood and lymphatic system disorders
Hemolysis	1/28 (3.6%)	1
Bleeding - Vaginal	1/28 (3.6%)	2
Bleeding - Lung	1/28 (3.6%)	1
Bleeding - GI	1/28 (3.6%)	1
Bleeding - CNS	1/28 (3.6%)	1
Cardiac disorders
Hypertension	2/28 (7.1%)	2
Tachycardia	1/28 (3.6%)	1
Cardiovascular, not otherwise specified	1/28 (3.6%)	1
Gastrointestinal disorders
Pancreatitis	1/28 (3.6%)	1
Mucositis	1/28 (3.6%)	1
Hepatobiliary disorders
Hyperbilirubinemia	6/28 (21.4%)	7
Infections and infestations
Fever of Unknown Origin	3/28 (10.7%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy	1/28 (3.6%)	1
Renal and urinary disorders
Renal Insufficiency	1/28 (3.6%)	1
Renal Failure, requiring dialysis	2/28 (7.1%)	2
Acute Kidney Injury	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/28 (3.6%)	1
Bronchospasm	1/28 (3.6%)	1
Acute Respiratory Distress Syndrome	1/28 (3.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.