Post-transplant Cyclophosphamide and Sirolimus Following Reduced Intensity Conditioning (RIC) Transplant

• Sponsor: Northside Hospital, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01244906
• Collaborator: Blood and Marrow Transplant Group of Georgia (Other)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 48
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial will evaluate the safety and efficacy of post-transplant Cy and sirolimus following reduced intensity allogeneic SCT. It is hoped that the combination of a reduced intensity preparative regimen with a calcineurin-free GVHD prophylaxis regimen will decrease the risk of acute and chronic GVHD, by both limiting mucosal toxicity and augmenting immune reconstitution, thereby improving the safety of the procedure. The past experience with post-transplant Cy suggests that SCT recipients will attain rapid donor T cell chimerism, which the investigators hope will translate into improved disease control through the well documented graft-versus-malignancy effects of donor T cells.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Neoplasms	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Post-Transplant Cyclophosphamide and Sirolimus for Graft-versus-host Disease (GVHD) Prophylaxis Following Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reduced Intensity Allogeneic Stem Cell Transplantation All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.

Outcome Measures

Primary Outcome Measures

1. Incidence of GVHD [1 year]

   To estimate the incidence of graft-versus-host disease (GVHD) when utilizing post-transplant cyclophosphamide (Cy) and sirolimus for GVHD prophylaxis following reduced intensity allogeneic hematopoietic stem cell transplantation (SCT) in patients with high risk hematologic malignancies.

Secondary Outcome Measures

1. Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment [Approximately Day 30]

   To estimate the incidence of neutrophil and platelet engraftment

2. Number of Participants With Non-Relapse Mortality [1 year]

3. Number of Patients With Disease Free Survival at 2 Years [2 years]

4. Number of Patients to Achieve Full Donor Chimerism [1 year]

   Characterize rate of achievement of full donor chimerism

5. Number of Patients With Overall Survival at 2 Years. [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Availability of a 7/8 or 8/8 (HLA-A, B, C, DR) related or unrelated donor

• Age 18-75

• One of the following high-risk malignancies

• Chronic Myelogenous Leukemia

• Acute Myelogenous Leukemia

• Myelodysplastic Syndrome

• Myelofibrosis

• Acute Lymphocytic Leukemia

• Acute Lymphoblastic Lymphoma

• Chronic Lymphocytic Leukemia

• Prolymphocytic Leukemia

• Low-grade non-Hodgkin's Lymphoma

• Mantle Cell Lymphoma

• Hodgkin Lymphoma

• Myeloma

Exclusion Criteria:

• Poor cardiac function (EF <40%)

• Poor pulmonary function (FEV1 and FVC <50% predicted)

• Poor liver function (bilirubin >/= 2 mg/dl not due to hemolysis, Gilbert's or primary malignancy)

• Poor renal function (creatinine >/= 2 mg/dl or creatinine clearance <40mL/min)

• Karnofsky status <70%

• HIV positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northside Hospital	Atlanta	Georgia	United States	30342

Sponsors and Collaborators

• Northside Hospital, Inc.
• Blood and Marrow Transplant Group of Georgia

Investigators

• Principal Investigator: Scott R Solomon, MD, Blood and Marrow Transplant Group of Georgia

Study Documents (Full-Text)

None provided.

More Information

Publications

• Basara N, Schulze A, Wedding U, Mohren M, Gerhardt A, Junghanss C, Peter N, Dölken G, Becker C, Heyn S, Kliem C, Lange T, Krahl R, Pönisch W, Fricke HJ, Sayer HG, Al-Ali H, Kamprad F, Niederwieser D; East German Study Group Hematology and Oncology (OSHO). Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission. Leukemia. 2009 Apr;23(4):635-40. doi: 10.1038/leu.2008.352. Epub 2009 Jan 8.
• Coenen JJ, Koenen HJ, van Rijssen E, Kasran A, Boon L, Hilbrands LB, Joosten I. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+ CD25+ FoxP3+ T cells. Bone Marrow Transplant. 2007 May;39(9):537-45. Epub 2007 Mar 12.
• de Witte T, Brand R, van Biezen A, Mufti G, Ruutu T, Finke J, von dem Borne P, Vitek A, Delforge M, Alessandrino P, Harlahakis N, Russell N, Martino R, Verdonck L, Kröger N, Niederwieser D; European Blood and Marrow Transplantation Group (EBMT), Chronic Leukemia Working Party (CLWP)-MDS subcommittee. Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: delay of the transplant is associated with inferior survival. Br J Haematol. 2009 Sep;146(6):627-36. doi: 10.1111/j.1365-2141.2009.07809.x. Epub 2009 Jul 14.
• Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003 Sep;9(9):1144-50. Epub 2003 Aug 17.
• Lehnert S, Rybka WB. Amplification of the graft-versus-host reaction by cyclophosphamide: dependence on timing of drug administration. Bone Marrow Transplant. 1994 Apr;13(4):473-7.
• Luznik L, Bolaños-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.
• Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant. 2002;8(3):131-8.
• Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001 Dec 1;98(12):3456-64.
• Mayumi H, Himeno K, Tanaka K, Tokuda N, Fan JL, Nomoto K. Drug-induced tolerance to allografts in mice. XII. The relationships between tolerance, chimerism, and graft-versus-host disease. Transplantation. 1987 Aug;44(2):286-90.
• Mayumi H. [Cyclophosphamide-induced immunological tolerance: an overview]. Nihon Geka Gakkai Zasshi. 1996 Dec;97(12):1097-108. Review. Japanese.
• Mielcarek M, Storer BE, Sandmaier BM, Sorror ML, Maloney DG, Petersdorf E, Martin PJ, Storb R. Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors. Biol Blood Marrow Transplant. 2007 Dec;13(12):1499-507.
• O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86.
• Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J, Keyvanfar K, Montero A, Hensel N, Kurlander R, Barrett AJ. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood. 2006 Aug 15;108(4):1291-7. Epub 2006 Apr 20.
• Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H, Steiner B, Berg E, Miehlke S, Bornhäuser M, Schneider T, Zeitz M, Stein H, Thiel E, Duchmann R, Uharek L. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood. 2006 Feb 15;107(4):1717-23. Epub 2005 Nov 8.
• Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997 May;15(5):1767-77.
• Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002 May 15;99(10):3493-9.
• Trenado A, Charlotte F, Fisson S, Yagello M, Klatzmann D, Salomon BL, Cohen JL. Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J Clin Invest. 2003 Dec;112(11):1688-96.
• Uberti JP, Ayash L, Braun T, Reynolds C, Silver S, Ratanatharathorn V. Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes. Bone Marrow Transplant. 2004 Sep;34(5):425-31.
• Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, Contag CH, Negrin RS. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006 Jul 1;108(1):390-9. Epub 2006 Mar 7.
• Zhao D, Zhang C, Yi T, Lin CL, Todorov I, Kandeel F, Forman S, Zeng D. In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease. Blood. 2008 Sep 1;112(5):2129-38. doi: 10.1182/blood-2008-02-140277. Epub 2008 Jun 12.
• Zorn E, Kim HT, Lee SJ, Floyd BH, Litsa D, Arumugarajah S, Bellucci R, Alyea EP, Antin JH, Soiffer RJ, Ritz J. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood. 2005 Oct 15;106(8):2903-11. Epub 2005 Jun 21.

• Responsible Party: Northside Hospital, Inc.
• ClinicalTrials.gov Identifier: NCT01244906
• Other Study ID Numbers: NSH 911
• First Posted: Nov 19, 2010
• Last Update Posted: May 1, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Northside Hospital, Inc.: Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Myelofibrosis; Acute Lymphocytic Leukemia; Acute Lymphoblastic Lymphoma; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Low-grade non-Hodgkin's Lymphoma; Mantle Cell Lymphoma; Hodgkin Lymphoma; Myeloma
• Additional relevant MeSH terms: Hematologic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Period Title: Overall Study
STARTED	26
COMPLETED	18
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Overall Participants	26
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	21 80.8%
>=65 years	5 19.2%
Sex: Female, Male (Count of Participants)
Female	10 38.5%
Male	16 61.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 19.2%
White	21 80.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	26 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of GVHD
Description	To estimate the incidence of graft-versus-host disease (GVHD) when utilizing post-transplant cyclophosphamide (Cy) and sirolimus for GVHD prophylaxis following reduced intensity allogeneic hematopoietic stem cell transplantation (SCT) in patients with high risk hematologic malignancies.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Measure Participants	26
Number [participants]	12 46.2%

2. Secondary Outcome

Title	Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment
Description	To estimate the incidence of neutrophil and platelet engraftment
Time Frame	Approximately Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Measure Participants	26
Number [participants]	26 100%

3. Secondary Outcome

Title	Number of Participants With Non-Relapse Mortality
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Measure Participants	26
Number [participants]	1 3.8%

4. Secondary Outcome

Title	Number of Patients With Disease Free Survival at 2 Years
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Measure Participants	26
Number [participants]	17 65.4%

5. Secondary Outcome

Title	Number of Patients to Achieve Full Donor Chimerism
Description	Characterize rate of achievement of full donor chimerism
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Measure Participants	26
Number [participants]	26 100%

6. Secondary Outcome

Title	Number of Patients With Overall Survival at 2 Years.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
Measure Participants	26
Number [participants]	19 73.1%

Adverse Events

Arm/Group Title	Reduced Intensity Allogeneic Stem Cell Transplantation
Arm/Group Description	All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. Allogeneic Hematopoietic Stem Cell Transplantation: Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.
All Cause Mortality
	Reduced Intensity Allogeneic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Reduced Intensity Allogeneic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	10/26 (38.5%)
Gastrointestinal disorders
Acute Cholecystitis	1/26 (3.8%)	1
GI bleeding	2/26 (7.7%)	2
Hepatobiliary disorders
VOD	1/26 (3.8%)	1
Investigations
Severe Hyperglycemia	1/26 (3.8%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia	3/26 (11.5%)	3
pulmonary embolism	1/26 (3.8%)	1
Vascular disorders
cellulitis	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	Reduced Intensity Allogeneic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	26/26 (100%)
Blood and lymphatic system disorders
neutropenia	26/26 (100%)
anemia	26/26 (100%)
enlarged lymph nodes	2/26 (7.7%)
lymphadenopathy	2/26 (7.7%)
febrile neutropenia	15/26 (57.7%)
petechiae	2/26 (7.7%)
thrombocytopenia	26/26 (100%)
leukopenia	26/26 (100%)
Cardiac disorders
bradycardia	6/26 (23.1%)
chest pressure	2/26 (7.7%)
hypertension	16/26 (61.5%)
hypotension	13/26 (50%)
orthostatic hypotension	2/26 (7.7%)
pleuritic chest pain	3/26 (11.5%)
tachycardia	17/26 (65.4%)
Ear and labyrinth disorders
ear fullness/pressure	2/26 (7.7%)
Eye disorders
blurry vision	4/26 (15.4%)
dry eyes	6/26 (23.1%)
periorbital edema	2/26 (7.7%)
periorbital redness	2/26 (7.7%)
Gastrointestinal disorders
Nausea	24/26 (92.3%)
abdominal bloating	8/26 (30.8%)
abdominal cramps	8/26 (30.8%)
abdominal discomfort/pain	14/26 (53.8%)
abdominal distention	13/26 (50%)
abdominal tenderness	5/26 (19.2%)
anorexia/decreased oral intake	11/26 (42.3%)
ascites	5/26 (19.2%)
bloody stool	2/26 (7.7%)
clostridium difficile colitis	4/26 (15.4%)
constipation	13/26 (50%)
decreased bowel movement frequency	2/26 (7.7%)
diarrhea	23/26 (88.5%)
dysphagia	7/26 (26.9%)
dry lips	2/26 (7.7%)
dry mouth	9/26 (34.6%)
epigastric pain	2/26 (7.7%)
esophagitis	2/26 (7.7%)
gas/flatulence	3/26 (11.5%)
GERD	19/26 (73.1%)
perirectal bleeding/hemorrhage	7/26 (26.9%)
hemorrhodial edema	2/26 (7.7%)
hemorrhodial pain	4/26 (15.4%)
hemorrhoids	7/26 (26.9%)
hyperactive bowel sounds	6/26 (23.1%)
stool incontinence	4/26 (15.4%)
malnutrition	2/26 (7.7%)
mouth sores	9/26 (34.6%)
mouth tenderness	10/26 (38.5%)
mucositis	15/26 (57.7%)
pain during defication	2/26 (7.7%)
throat pain	13/26 (50%)
perirectal irritation	4/26 (15.4%)
perirectal pain	4/26 (15.4%)
stomatitis	3/26 (11.5%)
vomiting	21/26 (80.8%)
General disorders
"cold sweats"	2/26 (7.7%)
"cold" feeling	2/26 (7.7%)
alopecia	3/26 (11.5%)
chills/rigors	14/26 (53.8%)
central venous catheter pain	15/26 (57.7%)
central venous catheter site drainage	5/26 (19.2%)
central venous catheter site erythema	8/26 (30.8%)
deconditioning	10/26 (38.5%)
facial edema	2/26 (7.7%)
fatigue	22/26 (84.6%)
fever	20/26 (76.9%)
lower-extremity edema	17/26 (65.4%)
lip edema	2/26 (7.7%)
peripheral edema	3/26 (11.5%)
seasonal allergies	9/26 (34.6%)
splenomegaly	2/26 (7.7%)
taste changes	7/26 (26.9%)
volume depletion	3/26 (11.5%)
generalized weakness	15/26 (57.7%)
Hepatobiliary disorders
increased alkaline phosphatase	17/26 (65.4%)
increased alanine aminotransferase	18/26 (69.2%)
increased aspartate aminotransferase	14/26 (53.8%)
hyperbilirubinemia	11/26 (42.3%)
perihepatic ascites	2/26 (7.7%)
veno-occlusive disease	2/26 (7.7%)
Immune system disorders
skin GVHD	11/26 (42.3%)
gut GVHD	2/26 (7.7%)
Infections and infestations
bacteremia	6/26 (23.1%)
BKV cystitis	12/26 (46.2%)
cellulitis	3/26 (11.5%)
CMV reactivation	2/26 (7.7%)
MRSE bacteremia	3/26 (11.5%)
staphylococcus epidermis bacteremia	2/26 (7.7%)
VRE positive	6/26 (23.1%)
Investigations
weight gain	5/26 (19.2%)
weight loss	12/26 (46.2%)
Metabolism and nutrition disorders
decreased appetite	18/26 (69.2%)
decreased fluid intake	5/26 (19.2%)
electrolyte wasting syndrome	2/26 (7.7%)
hypercalcemia	4/26 (15.4%)
hyperglycemia	26/26 (100%)
hyperkalemia	3/26 (11.5%)
hypernatremia	14/26 (53.8%)
hypoalbuminemia	20/26 (76.9%)
hypocalcemia	20/26 (76.9%)
hypoglycemia	2/26 (7.7%)
hypokalemia	18/26 (69.2%)
hypomagnesemia	16/26 (61.5%)
hyponatremia	9/26 (34.6%)
metabolic acidosis	2/26 (7.7%)
steroid-induced diabetes	6/26 (23.1%)
Musculoskeletal and connective tissue disorders
arm pain	3/26 (11.5%)
ataxia	11/26 (42.3%)
back pain	12/26 (46.2%)
bilateral knee pain	2/26 (7.7%)
generalized achiness	7/26 (26.9%)
hernia	2/26 (7.7%)
joint aches	3/26 (11.5%)
leg pain	2/26 (7.7%)
limited mobility	5/26 (19.2%)
muscle weakness	2/26 (7.7%)
hip pain	2/26 (7.7%)
foot pain	2/26 (7.7%)
lower-extremity pain	2/26 (7.7%)
neck pain	2/26 (7.7%)
pelvic pain	3/26 (11.5%)
shoulder pain	4/26 (15.4%)
ribcage tenderness	2/26 (7.7%)
suprapubic tenderness	2/26 (7.7%)
Nervous system disorders
dizziness	9/26 (34.6%)
drowsiness	12/26 (46.2%)
headache	16/26 (61.5%)
lethargy	10/26 (38.5%)
loss of coordination/balance	5/26 (19.2%)
neuropathy	7/26 (26.9%)
restless leg syndrome	2/26 (7.7%)
sedation	4/26 (15.4%)
sweats	6/26 (23.1%)
tremors	5/26 (19.2%)
unsteady gait	2/26 (7.7%)
visual changes	4/26 (15.4%)
Psychiatric disorders
agitation	3/26 (11.5%)
anxiety	21/26 (80.8%)
confusion	2/26 (7.7%)
depression	13/26 (50%)
flat affect	7/26 (26.9%)
hallucinations	2/26 (7.7%)
insomnia	13/26 (50%)
Renal and urinary disorders
bladder cramping	2/26 (7.7%)
bladder pain	7/26 (26.9%)
bladder spasms	6/26 (23.1%)
benign prostatic hyperplasia	2/26 (7.7%)
increased creatinine	9/26 (34.6%)
dysuria	16/26 (61.5%)
hematuria	12/26 (46.2%)
nocturia	2/26 (7.7%)
urinary frequency	15/26 (57.7%)
urinary hesitancy	3/26 (11.5%)
urinary incontinence	4/26 (15.4%)
urinary retention	5/26 (19.2%)
urinary urgency	6/26 (23.1%)
urinary tract infection	2/26 (7.7%)
Respiratory, thoracic and mediastinal disorders
dry cough	17/26 (65.4%)
coarse breath sounds	3/26 (11.5%)
decreased breath sounds	10/26 (38.5%)
epistaxis	8/26 (30.8%)
hemoptysis	3/26 (11.5%)
hypoxemic respiratory failure	2/26 (7.7%)
increased respiration rate	2/26 (7.7%)
lung crackles	10/26 (38.5%)
nasal congestion	10/26 (38.5%)
nasal drainage	7/26 (26.9%)
pain with breathing	3/26 (11.5%)
parainfluenza	3/26 (11.5%)
pleural effusion	6/26 (23.1%)
pneumonia	5/26 (19.2%)
post-nasal drip	4/26 (15.4%)
pulmonary infiltrates	5/26 (19.2%)
pulmonary nodules	2/26 (7.7%)
pulmonary opacites	4/26 (15.4%)
respiratory distress	3/26 (11.5%)
respiratory insufficiency	5/26 (19.2%)
rhinorrhea	6/26 (23.1%)
rhinovirus/URI	7/26 (26.9%)
rhonchi	5/26 (19.2%)
sinus congestion	7/26 (26.9%)
sinus drainage	14/26 (53.8%)
sinus pressure	3/26 (11.5%)
chronic sinusitis	4/26 (15.4%)
sneezing	2/26 (7.7%)
shortness of breath	15/26 (57.7%)
wheezing	8/26 (30.8%)
Skin and subcutaneous tissue disorders
bruising	10/26 (38.5%)
diaphoretic skin	2/26 (7.7%)
dry skin	10/26 (38.5%)
excoriation	3/26 (11.5%)
folliculitis	4/26 (15.4%)
generalized skin erythema	4/26 (15.4%)
hives	2/26 (7.7%)
hyperpigmentation	7/26 (26.9%)
oral erythema	3/26 (11.5%)
pale skin	3/26 (11.5%)
penile lesions	3/26 (11.5%)
pruritus	17/26 (65.4%)
rash	20/26 (76.9%)
skin abrasion	3/26 (11.5%)
skin color changes	3/26 (11.5%)
skin erythema	3/26 (11.5%)
skin lesions	4/26 (15.4%)
skin sensitivity	2/26 (7.7%)
skin tear	2/26 (7.7%)
skin tenderness	2/26 (7.7%)
Vascular disorders
deep venous thrombosis	2/26 (7.7%)
fluid overload	9/26 (34.6%)
facial flushing	4/26 (15.4%)
hematoma	2/26 (7.7%)
oral thrush	2/26 (7.7%)

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.