Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01341301
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 51.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancy	Radiation: Total Body Irradiation; Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Procedure: Allogeneic hematopoietic stem cell transplantation; Other: Laboratory biomarker analysis	Phase 2

Detailed Description

This is a phase II study in which patients receive a haploidentical HSCT from a single donor. The period between the donor lymphocyte infusion (DLI) and tolerizing doses of CY has been extended to allow for an increased period of allogeneic response against tumor targets. The outcomes of patients undergoing this extra time period will be compared to historical data to assess efficacy.

Primary Objective:

1. To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with an extra day inserted between the DLI and administration of cyclophosphamide (CY).

Secondary Objectives:

1. To assess the consistency and pace of engraftment.

2. To assess the pace of T cell and B cell immune recovery.

3. To assess regimen related toxicity, (GVHD) graft-versus-host disease incidence and severity, and overall survival in patients undergoing treatment on this protocol. .

4. To assess the tolerance of the period of fever, diarrhea, and rash in each arm in an effort to determine whether a longer interval prior to cytoxan changes this side effect qualitatively compared to prior patient groups or concurrent patient groups. N.B. Patients with hematologic malignancies in remission will continue to be transplanted without modification to the original 2-step approach and will serve as a concurrent comparison group.

5. To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens.

6. To determine the number of cluster of differentiation 4 (CD4+) cluster of differentiation 25 (CD25+) FOXP3+ regulatory cells post HSCT and to assess whether this is correlated with the development of GVHD after transplant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Human Leukocyte Antigen Partially-Matched Related Donor
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Nov 4, 2013
• Actual Study Completion Date: Aug 7, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Allogeneic HSCT CONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28.

Radiation: Total Body Irradiation; Undergo TBI; Other Names: TBI ; Biological: Donor Lymphocyte Infusion (DLI); Undergo DLI; Other Names: DLI ; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan Endoxan Endoxana Enduxan ; Drug: Tacrolimus; Given IV or PO; Other Names: Advagraf Prograf Protopic ; Drug: Mycophenolate mofetil; Given IV or PO; Other Names: Cellcept ; Procedure: Allogeneic hematopoietic stem cell transplantation; Undergo allogeneic HSCT; Other: Laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT) [1 year after undergoing hematopoietic stem cell transplant]

   To assess relapse free survival in participants undergoing Hematopoietic Stem Cell Transplant (HSCT) using the Thomas Jefferson University 2 step approach with an extra day inserted between the donor lymphocyte infusion (DLI) and administration of cyclophosphamide.

Secondary Outcome Measures

1. Pace of T-cell and B-cell Immune Recovery [Assessed up to 1 year]

   Reported descriptively

2. Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0 [Assessed up to 1 year]

   Reported descriptively

3. Incidence and Severity of GVHD, Graded According to Standard Criteria [Assessed up to 1 year]

   Reported descriptively

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete remission (CR).

Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (ie <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.

1. Patients must have at least one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci.

2. Patients must adequate organ function:

3. Left ventricular ejection fraction (LVEF) of >50 %

4. Diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) >50 % of predicted

5. Adequate liver function as defined by a serum bilirubin <1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times upper limit of normal

6. Creatinine clearance of > 60 ml/min

7. Karnofsky Performance Status of > 80% on the modified KPS tool

8. Patients must be willing to use contraception if they have childbearing potential.

9. Able to give informed consent

Exclusion Criteria:

1. Modified Karnofsky performance status (KPS) of <80%

2. 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index (HCT-CI) Index

3. Untreated class I or II antibodies against donor HLA antigens

4. HIV positive

5. Active involvement of the central nervous system with malignancy

6. Psychiatric disorder that would preclude patients from signing an informed consent

7. Pregnancy, or unwillingness to use contraception if they have child bearing potential

8. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder

9. Alemtuzumab treatment within 8 weeks of HSCT admission.

10. Anti-thymocyte globulin (ATG) level of > 2 ugm/ml

11. Patients with active inflammatory processes including Tmax >101 or active tissue inflammation are excluded

12. Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Cancer Center at Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

• Principal Investigator: Neal Flomenberg, MD, Thomas Jefferson University
• Principal Investigator: Dolores Grosso, DNP, CRNP, Thomas Jefferson University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

Publications

None provided.

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT01341301
• Other Study ID Numbers: 10D.06; 2009-41
• First Posted: Apr 25, 2011
• Last Update Posted: Apr 25, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Sidney Kimmel Cancer Center at Thomas Jefferson University: allogeneic stem cell transplant; TJU 2 Step; HSCT; Hematopoietic stem cell transplantation
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Mycophenolic Acid; Cyclophosphamide; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive Donor Lymphocyte Infusion (DLI) on day -6 and undergo cluster of differentiation (CD34+) selected allogeneic HSCT on day 0 Graft-versus-host disease (GVHD) PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo CD34+ selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	22 88%
>=65 years	3 12%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (13.6)
Sex: Female, Male (Count of Participants)
Female	8 32%
Male	17 68%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 12%
Not Hispanic or Latino	20 80%
Unknown or Not Reported	2 8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 24%
White	16 64%
More than one race	0 0%
Unknown or Not Reported	2 8%
Region of Enrollment (Count of Participants)
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT)
Description	To assess relapse free survival in participants undergoing Hematopoietic Stem Cell Transplant (HSCT) using the Thomas Jefferson University 2 step approach with an extra day inserted between the donor lymphocyte infusion (DLI) and administration of cyclophosphamide.
Time Frame	1 year after undergoing hematopoietic stem cell transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo CD34+ selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
Measure Participants	25
Count of Participants [Participants]	5 20%

2. Secondary Outcome

Title	Pace of T-cell and B-cell Immune Recovery
Description	Reported descriptively
Time Frame	Assessed up to 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo CD34+ selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
Measure Participants	0

3. Secondary Outcome

Title	Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0
Description	Reported descriptively
Time Frame	Assessed up to 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
Measure Participants	0

4. Secondary Outcome

Title	Incidence and Severity of GVHD, Graded According to Standard Criteria
Description	Reported descriptively
Time Frame	Assessed up to 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation (CD34+) selected allogeneic HSCT on day 0 Graft-versus-host disease (GVHD) PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
Measure Participants	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Allogeneic HSCT
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo CD34+ selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Total Body Irradiation: Undergo TBI Donor Lymphocyte Infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Tacrolimus: Given IV or PO Mycophenolate mofetil: Given IV or PO Allogeneic hematopoietic stem cell transplantation: Undergo allogeneic HSCT Laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Allogeneic HSCT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Allogeneic HSCT
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Hematuria	1/25 (4%)	1
Hyperbilirubinemia	2/25 (8%)	2
Hypoxia	4/25 (16%)	6
Syncope	1/25 (4%)	1
Cardiac disorders
Hypotension	1/25 (4%)	1
Left ventricular systolic dysfunction	1/25 (4%)	1
Ear and labyrinth disorders
Volume overload	1/25 (4%)	1
Gastrointestinal disorders
Cholecystitis	1/25 (4%)	1
CMV colitis	1/25 (4%)	1
CMV reactivation	2/25 (8%)	2
General disorders
Agitation	1/25 (4%)	1
Fevers	2/25 (8%)	3
Reintubation	1/25 (4%)	1
Infections and infestations
Sepsis	2/25 (8%)	2
Metabolism and nutrition disorders
Weight gain	1/25 (4%)	1
Psychiatric disorders
Depression	1/25 (4%)	1
Renal and urinary disorders
Acute kidney injury	1/25 (4%)	1
Acute renal failure	2/25 (8%)	2
Elevated liver enzymes	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/25 (8%)	2
Pneumonia	1/25 (4%)	1
Respiratory disease	1/25 (4%)	1
Respiratory failure	2/25 (8%)	2
Other (Not Including Serious) Adverse Events
	Allogeneic HSCT
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Bacteremia	3/25 (12%)	4
Hematoma	1/25 (4%)	1
Hemochromatosis	1/25 (4%)	1
Hyperbilirubinemia	8/25 (32%)	8
Hypercholesterolemia	1/25 (4%)	1
Hyperglycemia	1/25 (4%)	1
Hyperkalemia	1/25 (4%)	1
Hypernatremia	2/25 (8%)	2
Increased creatinine	1/25 (4%)	1
Leukopenia	2/25 (8%)	2
Thrombus	1/25 (4%)	1
Cardiac disorders
Atrial fibrillation	1/25 (4%)	1
Bradycardia	1/25 (4%)	1
Deep vein thrombosis	1/25 (4%)	1
Dysarthria	1/25 (4%)	1
Non-ST segment elevation myocardial infarction	1/25 (4%)	1
Pericardial effusion	1/25 (4%)	1
Pericarditis	1/25 (4%)	1
Sinus tachycardia	2/25 (8%)	2
Tachycardia	14/25 (56%)	17
Ventricular trigeminy	1/25 (4%)	1
Ear and labyrinth disorders
Difficulty hearing	1/25 (4%)	1
Eye disorders
Black eye	1/25 (4%)	1
Blurry vision	2/25 (8%)	3
Change in vision	1/25 (4%)	1
Eye dryness	1/25 (4%)	1
Eye pain	1/25 (4%)	1
Red eyes	1/25 (4%)	1
Tearing of eyes	1/25 (4%)	1
Gastrointestinal disorders
Clostridium difficile	1/25 (4%)	1
Constipation	7/25 (28%)	7
Diarrhea	15/25 (60%)	21
Epigastric pain	2/25 (8%)	2
Esophagitis	2/25 (8%)	2
Gas pain	1/25 (4%)	1
Gastroesophageal reflux disease	1/25 (4%)	1
Hemorrhoids	1/25 (4%)	1
Hernia	1/25 (4%)	1
Indigestion	2/25 (8%)	2
Nausea	20/25 (80%)	21
General disorders
Arthritis	1/25 (4%)	1
Blister	1/25 (4%)	1
Chest discomfort	3/25 (12%)	3
Chest pain	5/25 (20%)	5
Chills/rigors	10/25 (40%)	12
CMV reactivation	5/25 (20%)	5
Confusion	5/25 (20%)	5
Congestion	3/25 (12%)	3
Cough	8/25 (32%)	9
Crackles	1/25 (4%)	1
Diaphoresis	1/25 (4%)	1
Dizziness	3/25 (12%)	3
Dry mouth	4/25 (16%)	4
Dysgeusia	1/25 (4%)	1
Dysphagia	3/25 (12%)	3
Edema	12/25 (48%)	16
Electrolyte imbalance	6/25 (24%)	8
Elevated alkaline phosphatase	1/25 (4%)	1
Epistaxis	1/25 (4%)	1
Facial pain	1/25 (4%)	1
Fatigue	9/25 (36%)	10
Feet/ankle swelling	2/25 (8%)	2
Fevers	17/25 (68%)	30
Flank pain	2/25 (8%)	2
General pain	1/25 (4%)	1
Hand/foot tightness	1/25 (4%)	1
Headache	12/25 (48%)	17
Hiccups	2/25 (8%)	2
Hip pain	2/25 (8%)	2
Hives	4/25 (16%)	4
Hoarseness	1/25 (4%)	1
Hyperglycemia	1/25 (4%)	1
Hyperkalemia	1/25 (4%)	1
Hypertension	10/25 (40%)	12
Hypervolemia	5/25 (20%)	5
Hypokalemia	2/25 (8%)	3
Hyponatremia	2/25 (8%)	2
Hypotension	12/25 (48%)	14
Hypoxia	6/25 (24%)	6
Insomnia	8/25 (32%)	8
Intolerance to cold	1/25 (4%)	1
Joint swelling	1/25 (4%)	1
Joint pain	1/25 (4%)	1
Lethargy	5/25 (20%)	5
Lung effusion	1/25 (4%)	1
Malaise	2/25 (8%)	2
Mucositis	13/25 (52%)	13
Neck pain	1/25 (4%)	1
Neck swelling	1/25 (4%)	1
Nocturia	2/25 (8%)	2
Odynophagia	2/25 (8%)	2
Oral discomfort	3/25 (12%)	3
Oral pain	2/25 (8%)	2
Parasthesia	3/25 (12%)	3
Parotid glad pain	1/25 (4%)	1
Pelvic pain	1/25 (4%)	1
Peripheral edema	1/25 (4%)	1
Peri-rectal discomfort	1/25 (4%)	1
Rhinorrhea	1/25 (4%)	1
Sialadenitis	1/25 (4%)	1
SIRS	1/25 (4%)	1
Somnolence	1/25 (4%)	1
Sore on tip of penis	1/25 (4%)	1
Sore throat	7/25 (28%)	7
Supraventricular tachycardia	1/25 (4%)	1
Temporal wasting	1/25 (4%)	1
Tenderness	1/25 (4%)	1
Thrush	1/25 (4%)	1
Tongue pain	2/25 (8%)	2
Tracheal pain	1/25 (4%)	1
Transfusion reaction event	1/25 (4%)	1
Vivid dreams	1/25 (4%)	1
Volume overload	4/25 (16%)	4
Vomiting	7/25 (28%)	7
Infections and infestations
BK viremia	2/25 (8%)	2
CMV viremia	1/25 (4%)	1
HHV6 viremia	3/25 (12%)	3
Infection, other	2/25 (8%)	2
Sepsis	1/25 (4%)	1
Metabolism and nutrition disorders
Anorexia	1/25 (4%)	1
Decreased appetite	5/25 (20%)	5
Metabolism disorder, other	3/25 (12%)	3
Weight loss	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Abdominal discomfort	2/25 (8%)	2
Abdominal pain	8/25 (32%)	10
Agitation	5/25 (20%)	5
Ankle pain	1/25 (4%)	1
Arm pain	2/25 (8%)	2
Arm swelling	1/25 (4%)	1
Back pain	5/25 (20%)	6
Bone pain	2/25 (8%)	3
Calf pain	1/25 (4%)	1
Hip pain	2/25 (8%)	2
Leg tightness	1/25 (4%)	1
Muscle cramps	1/25 (4%)	1
Muscle pain	1/25 (4%)	1
Neck discomfort	1/25 (4%)	1
Wrist pain	1/25 (4%)	1
Nervous system disorders
Aphasia	1/25 (4%)	1
Depression	1/25 (4%)	1
Mental status change	2/25 (8%)	2
Neuropathy	3/25 (12%)	3
Polyneuromyopathy	1/25 (4%)	1
Restless leg	1/25 (4%)	1
Seizures	1/25 (4%)	1
Tremors	3/25 (12%)	3
Weakness	1/25 (4%)	1
Psychiatric disorders
Anxiety	8/25 (32%)	9
Hallucinations	2/25 (8%)	2
Renal and urinary disorders
Abnormal LFTs	2/25 (8%)	2
Acute kidney injury	4/25 (16%)	4
Benign prostatic hyperplasia	1/25 (4%)	1
Cystitis	1/25 (4%)	1
Decreased urine output	2/25 (8%)	2
Dysuria	4/25 (16%)	4
Elevated liver enzymes	1/25 (4%)	1
Hematuria	5/25 (20%)	5
Proteinuria	3/25 (12%)	3
Urinary frequency	1/25 (4%)	1
Urinary incontinence	4/25 (16%)	4
Urinary retention	4/25 (16%)	4
Reproductive system and breast disorders
Vaginal discharge	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Blood-tinged sputum	1/25 (4%)	1
Difficulty breathing	1/25 (4%)	1
Dry cough	1/25 (4%)	1
Dyspnea	4/25 (16%)	4
Orthopnea	1/25 (4%)	1
Pneumonia	5/25 (20%)	5
Pulmonary edema	1/25 (4%)	2
Pulmonary infiltrates	1/25 (4%)	1
Respiratory failure	1/25 (4%)	1
Tachypnea	5/25 (20%)	5
Upper respiratory tract infection symptoms	1/25 (4%)	1
Wheezing	2/25 (8%)	3
Skin and subcutaneous tissue disorders
Dry skin	2/25 (8%)	2
Hives	4/25 (16%)	4
Itchiness	1/25 (4%)	1
Lesions	1/25 (4%)	1
Lip swelling	2/25 (8%)	2
Pruritis	1/25 (4%)	1
Rash	15/25 (60%)	22
Skin pain	1/25 (4%)	1
Skin wound	1/25 (4%)	1
Subcutaneous emphysema	1/25 (4%)	1
Vascular disorders
Orthostatic hypotension	1/25 (4%)	1
Pericatheter DVT	1/25 (4%)	1
Petechia	1/25 (4%)	2
Phlebitis	1/25 (4%)	1
Pleural effusion	3/25 (12%)	3
Thromboembolic event	1/25 (4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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