Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00691015
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 48
• Location: 1
• Arm: 1
• Duration (Months): 71
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and antithymocyte globulin before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms	Biological: rituximab; Drug: busulfan; Drug: carmustine; Drug: cyclophosphamide; Drug: cytarabine; Drug: etoposide; Drug: fludarabine phosphate; Drug: melphalan; Radiation: total body irradiation (TBI); Drug: anti-thymocyte globulin IV	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the incidence and severity of acute graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies treated with immunosuppressive therapy comprising sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis.

• To determine the safety of this regimen in these patients at 6 months after PBSCT.

Secondary

• To determine the time to engraftment (i.e., platelet and absolute neutrophil recovery) in patients treated with this regimen.

• To determine the length of hospital stay of these patients within 100 days after PBSCT.

• To determine the incidence of infections, including CMV and EBV reactivation and post-transplant lymphoproliferative disorders, in patients treated with this regimen.

• To determine the incidence of thrombotic microangiopathy and veno-occlusive disease in patients treated with this regimen.

• To determine the incidence of chronic GVHD in patients treated with this regimen.

• To determine the overall and disease-free survival of these patients at 2 years after PBSCT.

• To determine the Karnofsky performance status of these patients at baseline and at various time points after PBSCT.

• To conduct immunocorrelative studies prior to and at various time points after PBSCT.

OUTLINE:

• Conditioning regimen: Patients receive 1 of 6 conditioning regimens (standard of care treatment) between days -9 and -3, based on diagnosis and the treating physician's preference regarding regimen intensity.

• Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.

• Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV.

• Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV.

• Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV.

• Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV.

• Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.

• Allogeneic peripheral blood stem cell transplantation: Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.

• Graft-versus-host disease prophylaxis (GVHD): Patients receive tacrolimus IV continuously over 24 hours or orally and sirolimus orally beginning on day -3 and continuing until day 30 or day 90, followed by a taper in the absence of GVHD. Patients also receive anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.

Blood samples are obtained at baseline and periodically during study for correlative biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution, T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after transplantation, and regulatory T-cell reconstitution.

After completion of study therapy, patients are followed periodically for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Chemotherapy or chemotherapy + total body irradiation Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV.

Biological: rituximab; Given IV; Other Names: Rituxan MabThera Zytux ; Drug: busulfan; Given IV; Other Names: Busulfex Myleran ; Drug: carmustine; Given IV; Other Names: Bicnu Gliadel ; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan Cytoxan Lyophilized Neosar ; Drug: cytarabine; Given IV; Other Names: Depocyt ; Drug: etoposide; Given IV; Other Names: Etopophos Toposar ; Drug: fludarabine phosphate; Given IV; Other Names: Fludara® ; Drug: melphalan; Given IV; Other Names: Alkeran ; Radiation: total body irradiation (TBI); Given once or twice daily; Other Names: radiotherapy ; Drug: anti-thymocyte globulin IV; Given IV; Other Names: Thymoglobulin

Outcome Measures

Primary Outcome Measures

1. Incidence of Acute Graft-versus-host Disease (GVHD) [Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria]

2. Severity of Acute Graft-versus-host Disease (GVHD) [Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria]

3. Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment. [Within 6 months after PBSCT]

Secondary Outcome Measures

1. Incidence of Chronic GVHD. [Within 2 years after PBSCT]

2. Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] ) [post transplant, up to 4 weeks]

3. Overall Survival. [At 2 years after PBSCT]

4. Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders) [Within 6 months after PBSCT]

5. Karnofsky Performance Status Performance Status [At 90 days after PBSCT]

   100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of a hematological malignancy, including any of the following:

• Non-Hodgkin lymphoma in complete remission (CR) or partial remission (PR)

• Hodgkin lymphoma in CR or PR

• Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting either of the following criteria:

• In CR

• Not in CR and meets the following criteria:

• Bone marrow blast < 20% within 4 weeks of transplantation

• Peripheral blood absolute blast count < 500 per microliter on the day of initiating conditioning therapy

• Myelodysplastic syndromes, treated or untreated

• Chronic myeloid leukemia in chronic phase or accelerated phase

• Multiple myeloma in CR or PR

• Chronic lymphocytic leukemia in second or greater CR or PR

• Myelofibrosis or other myeloproliferative disorders meeting the following criteria:

• Bone marrow blasts < 20% within 4 weeks of transplantation

• Peripheral blood absolute blast count < 500 per microliter on the day of initiating conditioning therapy

• Patients with ascites not allowed

• No prior bone marrow or ex vivo engineered or processed graft (i.e., CD34+ enrichment, T-cell depletion, etc)

• Scheduled to undergo peripheral blood stem cell transplantation from a suitable HLA-matched or -mismatched unrelated donor, as determined by treating physician

• High resolution molecular HLA typing is required for HLA class I and II

• No more than one antigen or allele mismatch

• No documented uncontrolled CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2

• Karnofsky PS 60-100%

• Creatinine clearance > 50 mL/min

• Bilirubin < 3 times upper limit of normal (ULN)

• ALT and AST < 3 times ULN

• LVEF > 50%

• FVC, FEV_1, or DLCO > 50% predicted

• Patients on home oxygen not allowed

• Able to cooperate with oral medication intake

• HIV negative

• No active hepatitis B or hepatitis C

• No known contraindication to sirolimus, tacrolimus, or anti-thymocyte globulin

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Study Chair: Zaid Al-Kadhimi, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zaid Al-Kadhimi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00691015
• Other Study ID Numbers: 2007-127; P30CA022453; GENZ-WSU-2007-127; 2007-127
• First Posted: Jun 5, 2008
• Last Update Posted: Jun 28, 2017
• Last Verified: May 1, 2017

• Keywords provided by Zaid Al-Kadhimi, Principal Investigator, Barbara Ann Karmanos Cancer Institute: stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult Hodgkin lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III small lymphocytic lymphoma; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); chronic phase chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; secondary acute myeloid leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; primary myelofibrosis; atypical chronic myeloid leukemia, BCR-ABL negative; chronic eosinophilic leukemia; chronic myelomonocytic leukemia; chronic neutrophilic leukemia
• Additional relevant MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Syndrome; Cytarabine; Cyclophosphamide; Melphalan; Busulfan; Carmustine; Rituximab; Fludarabine; Fludarabine phosphate; Etoposide; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	Conditioning Regimen
Arm/Group Description	Chemotherapy or chemotherapy + total body irradiation Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
Period Title: Overall Study
STARTED	48
COMPLETED	47
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together. Standard of Care (SOC) Chemotherapy or Standard of Care (SOC) Chemotherapy + total body irradiation SOC chemotherapy or SOC chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
Overall Participants	47
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	17 36.2%
Male	30 63.8%
Region of Enrollment (participants) [Number]
United States	47 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Acute Graft-versus-host Disease (GVHD)
Time Frame	Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	44.7 95.1%

2. Primary Outcome

Title	Severity of Acute Graft-versus-host Disease (GVHD)
Time Frame	Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria

Outcome Measure Data

Analysis Population Description

The patients that contracted sever acute graph versus host disease (aGVHD) from those who developed aGVHD

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	21
Number (90% Confidence Interval) [% of participants with severe aGVHD]	33.3 70.9%

3. Primary Outcome

Title	Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.
Time Frame	Within 6 months after PBSCT

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Number (95% Confidence Interval) [% of participants with a reported SAE]	93.62 199.2%

4. Secondary Outcome

Title	Incidence of Chronic GVHD.
Time Frame	Within 2 years after PBSCT

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Number (95% Confidence Interval) [percentage of participants]	44.68 95.1%

5. Secondary Outcome

Title	Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )
Time Frame	post transplant, up to 4 weeks

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Median (Full Range) [Days]	11

6. Secondary Outcome

Title	Overall Survival.
Time Frame	At 2 years after PBSCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Number (95% Confidence Interval) [percentage of participants]	57.4 122.1%

7. Secondary Outcome

Title	Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)
Time Frame	Within 6 months after PBSCT

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Number (95% Confidence Interval) [percentage of participants]	80.85 172%

8. Secondary Outcome

Title	Karnofsky Performance Status Performance Status
Description	100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
Time Frame	At 90 days after PBSCT

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	All Participants
Arm/Group Description	All regimens were analyzed together.
Measure Participants	47
Median (Full Range) [units on a scale]	80

Adverse Events

Arm/Group Title	Conditioning Regimen
Arm/Group Description	Chemotherapy or chemotherapy + total body irradiation Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
All Cause Mortality
	Conditioning Regimen
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Conditioning Regimen
	Affected / at Risk (%)	# Events
Total	44/47 (93.6%)
Blood and lymphatic system disorders
Blood/Bone Marrow	1/47 (2.1%)	1
Disseminated intravascular coagulation	1/47 (2.1%)	1
Febrile neutropenia	1/47 (2.1%)	1
Leukocytes	12/47 (25.5%)	12
Lymphopenia	11/47 (23.4%)	11
Cardiac disorders
Cardiac ischemia/infarction	3/47 (6.4%)	3
Cardiopulmonary arrest	2/47 (4.3%)	2
Left Ventricular diastolic dysfunction	1/47 (2.1%)	1
Left Ventricular systolic dysfunction	1/47 (2.1%)	1
Pain-Cardiovascular-cardiac/heart	1/47 (2.1%)	1
Pericardial effusion	1/47 (2.1%)	1
Supraventricular and nodal arrhythmia	2/47 (4.3%)	2
Tachycardia	1/47 (2.1%)	1
Ventricular arrhythmia-ventricular tachycardia	1/47 (2.1%)	1
Gastrointestinal disorders
Ascites	4/47 (8.5%)	4
Colitis	7/47 (14.9%)	7
Diarrhea	6/47 (12.8%)	6
Gastritis	2/47 (4.3%)	2
Hemorrhage, GI-Liver	1/47 (2.1%)	1
Ileus	1/47 (2.1%)	1
Mucositis/stomatis-large bowel	2/47 (4.3%)	2
Mucositis/stomatis-Small bowel	1/47 (2.1%)	1
Nausea	7/47 (14.9%)	7
Pain-Gastrointestinal-Abdominal NOS	1/47 (2.1%)	1
Pain-Gastrointestinal-oral cavity	4/47 (8.5%)	4
Pain-gastrointestinal-stomach	1/47 (2.1%)	1
Vomiting	3/47 (6.4%)	3
General disorders
Fatigue	1/47 (2.1%)	1
Fever	1/47 (2.1%)	1
Hemorrhage, GI	4/47 (8.5%)	4
Rigors/chills	2/47 (4.3%)	2
Death-disease progression	2/47 (4.3%)	2
Death-disease progression NOS	1/47 (2.1%)	1
Death-GVHD	1/47 (2.1%)	1
Death SOS	1/47 (2.1%)	1
Death-cGVHD	3/47 (6.4%)	3
Death-aGVHD/infection	1/47 (2.1%)	1
Death-Multi organ failure	2/47 (4.3%)	2
Death-Multi organ failure/SOS	1/47 (2.1%)	1
Death-pancytopenia possible bleed	1/47 (2.1%)	1
Death-Disease progression (from 2nd BMT not associated with this protocol)	1/47 (2.1%)	1
Death-aGVHD	1/47 (2.1%)	1
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other (VOD/SOS)	3/47 (6.4%)	3
Liver Dysfunction/Failure	1/47 (2.1%)	1
Immune system disorders
Cytokine release syndrome	1/47 (2.1%)	1
Infections and infestations
Infection	24/47 (51.1%)	24
Infection BK	6/47 (12.8%)	6
Infection CMV	6/47 (12.8%)	6
Infection EBV	4/47 (8.5%)	4
Infection HSV	2/47 (4.3%)	2
Infection VZV in CSF	1/47 (2.1%)	1
Infections aspergillus	2/47 (4.3%)	2
Infection Pulmonary	1/47 (2.1%)	1
infection, with normal ANC	11/47 (23.4%)	11
Infection-Pulmonary/Upper Resp.	2/47 (4.3%)	2
Death-Multi organ failure/Sepsis	2/47 (4.3%)	2
Injury, poisoning and procedural complications
Fracture	1/47 (2.1%)	1
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	1/47 (2.1%)	1
Investigations
alanine aminotransferase (ALT) increased	6/47 (12.8%)	6
alanine aminotransferase (ALT), SGPT	2/47 (4.3%)	2
aspartate aminotransferase (AST) increased	7/47 (14.9%)	7
aspartate aminotransferase (AST) increased, SGOT	2/47 (4.3%)	2
Alkaline Phosphatase increased	2/47 (4.3%)	2
Bilirubin increased	9/47 (19.1%)	9
Cardiac troponin I increased	3/47 (6.4%)	3
Creatinine increased	7/47 (14.9%)	7
Hemoglobin	11/47 (23.4%)	11
Lipase	2/47 (4.3%)	2
Lymphocytes	3/47 (6.4%)	3
Neutrophils	11/47 (23.4%)	11
Platelets	12/47 (25.5%)	12
prolonged intubation	3/47 (6.4%)	3
Metabolism and nutrition disorders
Acidosis	4/47 (8.5%)	4
Anorexia	6/47 (12.8%)	6
Calcium serum - low	6/47 (12.8%)	6
Glucose	1/47 (2.1%)	1
Hyperglycemia	12/47 (25.5%)	12
Iron Overload	6/47 (12.8%)	6
Magnesium, Serum high	2/47 (4.3%)	2
Magnesium, Serum low	1/47 (2.1%)	1
Potassium, Serum high	7/47 (14.9%)	7
Potassium, serum low	4/47 (8.5%)	4
Sodium, Serum-low	4/47 (8.5%)	4
Musculoskeletal and connective tissue disorders
Arthritis	1/47 (2.1%)	1
Pain-mid/back, hip	1/47 (2.1%)	1
Pain-Musculoskeletal-Back	1/47 (2.1%)	1
Pain-Musculoskeletal-Bone	1/47 (2.1%)	1
pain-chest wall	1/47 (2.1%)	1
Nervous system disorders
CNS cerebrovascular ischemia	1/47 (2.1%)	1
Encephalopathy	1/47 (2.1%)	1
Other-Right side facial droop	1/47 (2.1%)	1
Pain-Neurology-head/headache	2/47 (4.3%)	2
Pain-Neurology-headache	1/47 (2.1%)	1
Somnolence/depressed level of consciousness	4/47 (8.5%)	4
Psychiatric disorders
Confusion	5/47 (10.6%)	5
mood alteration	1/47 (2.1%)	1
Renal and urinary disorders
pain-renal/genitourinary	1/47 (2.1%)	1
Renal-other-Acute Renal Failure	5/47 (10.6%)	5
Respiratory, thoracic and mediastinal disorders
Acute Respiratory distress	2/47 (4.3%)	2
Dyspnea	4/47 (8.5%)	4
Hemorrhage, pulmonary/upper respiratory	2/47 (4.3%)	2
Hemorrhage, pulmonary/upper respiratory/lung	3/47 (6.4%)	3
Hypoxia	11/47 (23.4%)	11
Pain Pulmonary/Respiratroy-throat/pharynx/larynx	1/47 (2.1%)	1
Pleural effusion	2/47 (4.3%)	2
Pneumonitis/pulmonary infiltrates	8/47 (17%)	8
Pulmonary Edema	2/47 (4.3%)	2
Pulmonary Hypertension	2/47 (4.3%)	2
Death-intersititial pneumonia	1/47 (2.1%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin - palmar erythema	1/47 (2.1%)	1
Rash	1/47 (2.1%)	1
Rash/Desquamation	10/47 (21.3%)	10
Vascular disorders
Hypertension	4/47 (8.5%)	4
Hypotension	3/47 (6.4%)	3
Thrombosis/embolism (vascular access-related)	2/47 (4.3%)	2
Thrombosis/embolism/thrombus	1/47 (2.1%)	1
Thrombosis/embolism (left lower extremity)	1/47 (2.1%)	1
Thrombosis/embolism (pulmonary)	1/47 (2.1%)	1
Thrombotic microangiopathy	4/47 (8.5%)	4
Other (Not Including Serious) Adverse Events
	Conditioning Regimen
	Affected / at Risk (%)	# Events
Total	0/47 (0%)

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.