Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01350245
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arm: 1
• Duration (Months): 46
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary hypothesis of this research study is that patients in remission undergoing myeloablative haploidentical hematopoietic stem cell transplantation (HSCT) on the Thomas Jefferson University (TJU) 2 Step treatment regimen will have a disease-free survival (DFS) rate at 1 year that is the same or better than the historical DFS of patients with similar diagnoses and ages undergoing matched sibling HSCT. Based on a review of the literature a DFS rate of 50% or better at 1 year would meet the criterion for an effective alternative therapy. A DFS rate of 75% or better would imply superior efficacy of the TJU 2 Step approach over T-replete matched sibling HSCT.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia	Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil (MMF); Drug: Tacrolimus; Device: Hematopoietic stem cell transplantation (HSCT)	Phase 2

Detailed Description

The primary rationale for the development of this research study is to find out if the Thomas Jefferson University (TJU) 2 Step approach to stem cell transplant is an effective treatment for patients with blood cancers who require transplant for long-term survival but are without an available matched-sibling donor. Historically, survival rates for patients undergoing half-matched stem cell transplant have been much lower than those observed after matched sibling stem cell transplant. This may be due to the poor-risk disease features of the patients by the time they are referred for hematopoietic stem cell transplantation (HSCT). Survival post half-matched stem cell transplant has also been affected by the requirement to remove or soothe donor T cells resulting in higher rates of infection and relapse. Newer approaches to haploidentical HSCT, such as the TJU 2 Step approach, utilize cyclophosphamide (CY) to tolerize donor lymphocytes instead of removing them completely from the donor product. This has resulted in less infection without concomitant increase in severe graft-versus-host disease (GVHD) and has increased overall survival as compared to older haploidentical treatment approaches due to decreases in regimen-related morbidity.

Because of the historically low overall survival (OS) after haploidentical HSCT, it has become a procedure of last resort with most centers unwilling to consider it unless all other options are exhausted. With the recent development of regimens such as the TJU 2 Step approach which provide safe, alternative platforms for HSCT, it is now feasible, and ethically more acceptable, for patients without matched sibling donors to undergo HSCT prior to being heavily pretreated or developing resistant disease. In this setting, i.e. equivalent regimen safety profiles and more homogenous patient comparison groups, it is possible to more accurately compare antitumor effects between matched sibling donors and haploidentical donors. There is ample evidence in the literature that HLA mismatching causes GVHD. There is not a large body of evidence supporting the notion that HLA mismatching provides superior tumor control translating into greater relapse free survival. As compared to more common types of transplants where donor T cells are given to the recipient, the investigators would surmise that the T cell tolerization associated with the TJU 2 Step approach may decrease the anti-tumor effects of the donor immune system. Conversely, the greater degree of human leukocyte antigen (HLA) mismatch with exploitation of NK effects may mitigate some of the attenuated T cell alloreactivity.

Thus, in the context of comparable regimen-related toxicity, our major aim in this research study is to compare graft versus tumor effects as measured by disease-free survival (DFS) between matched sibling HSCT and the TJU 2 Step haploidentical HSCT. If DFS is similar despite T cell tolerization, than the TJU 2 Step haploidentical approach should be considered an effective alternative therapy for those patients in remission without a matched sibling donor. The widespread benefit of this outcome would be the enfranchisement of segments of the population who are without available matched donors resulting in a delay or a failure to receive this potentially life-saving therapy. If DFS survival after treatment on the TJU 2 Step haploidentical approach is superior to what would be expected after matched sibling HSCT, then one could conclude that haploidentical HSCT confers greater tumor control forming the basis for future studies regarding the potential benefits of utilizing haploidentical donors over matched sibling donors when both types of donors are available.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 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 Patients With Hematologic Malignancies in Remission From HLA Partially-Matched Related Donors
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: TJU 2 Step Regimen All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone.

Radiation: Total Body Irradiation (TBI); Total body irradiation is given in 8 fractions over 4 days (total dose of 12 Gy).; Biological: Donor Lymphocyte Infusion (DLI); After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days.; Drug: Cyclophosphamide; Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days; Other Names: Endoxan Cytoxan Neosar Procytox Revimmune cytophosphane ; Drug: Mycophenolate Mofetil (MMF); Started the day before the transplant to prevent graft versus host disease (GVHD); Other Names: CellCept ; Drug: Tacrolimus; Started the day before the transplant to prevent graft-versus-host disease (GVHD); Other Names: FK-506 Fujimycin ; Device: Hematopoietic stem cell transplantation (HSCT); One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-donor stem cell product. This is the day of transplant. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.; Other Names: CliniMACS

Outcome Measures

Primary Outcome Measures

1. Disease-Free Survival (DFS) [1 year post-transplant]

   1-year post-transplant disease free survival (DFS), defined as success if a patient is alive and disease free at 1-year post-transplant.

2. Probability of Overall Survival at 15 Months Post-treatment [15 months]

   Probability of overall survival at 15 months post-treatment, defined as success if a patient is alive 1-year post-transplant.

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 or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.

• Diagnoses include:

Acute Myeloid Leukemia Myelodysplastic Syndromes Biphenotypic Leukemia Acute Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Lymphocytic Leukemia Plasma Cell Neoplasms Lymphoma Hodgkin Disease Aplastic Anemia

1. Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.

2. Patients must adequate organ function:

• LVEF of > or = 50%

• DLCO > or = 50% of predicted corrected for hemoglobin

• Adequate liver function as defined by a serum bilirubin < or = 1.8, AST or ALT < or = 2.5X upper limit of normal

• Creatinine clearance of > or = 60 ml/min

1. Performance status > or = 70% (TJU Karnofsky)

2. HCT-CI Score < 5 Points

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

4. Able to give informed consent

Exclusion Criteria:

1. Performance status < or = 70% (TJU Karnofsky)

2. HCT-CI Score > 5 Points

3. Combination of Performance status of < 80% (TJU Karnofsky) and an HCT-CI of 4 points or more.

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

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

9. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of > or = 2 ugm/ml

10. Patients who cannot receive cyclophosphamide

11. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

• Principal Investigator: Dolores Grosso, DNP, CRNP, Thomas Jefferson University
• Principal Investigator: Neal Flomenberg, MD, 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: NCT01350245
• Other Study ID Numbers: 10D.219; 2010-10
• First Posted: May 9, 2011
• Last Update Posted: Nov 29, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Sidney Kimmel Cancer Center at Thomas Jefferson University: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia; Hematopoietic stem cell transplant (HSCT); myeloablative haploidentical HSCT; graft versus host disease (GVHD)
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Neoplasms, Plasma Cell; Multiple Myeloma; Plasmacytoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Anemia, Aplastic; Mycophenolic Acid; Cyclophosphamide; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	TJU 2 Step Regimen
Arm/Group Description	All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone. Total Body Irradiation (TBI): Total body irradiation given in 8 fractions over 4 days (total dose of 12 Gy). Donor Lymphocyte Infusion (DLI): After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days. Cyclophosphamide: Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days Mycophenolate Mofetil (MMF): Started the day before the transplant to prevent graft versus host disease (GVHD) Tacrolimus: Started the day before the transplant to prevent graft-versus-host disease (GVHD) Hematopoietic stem cell transplantation (HSCT): One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-do
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TJU 2 Step Regimen
Arm/Group Description	All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone. Total Body Irradiation (TBI): Total body irradiation given in 8 fractions over 4 days (total dose of 12 Gy). Donor Lymphocyte Infusion (DLI): After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days. Cyclophosphamide: Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days Mycophenolate Mofetil (MMF): Started the day before the transplant to prevent graft versus host disease (GVHD) Tacrolimus: Started the day before the transplant to prevent graft-versus-host disease (GVHD) Hematopoietic stem cell transplantation (HSCT): One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-do
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.2 (14.3)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 96.4%
>=65 years	1 3.6%
Sex: Female, Male (Count of Participants)
Female	8 28.6%
Male	20 71.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 7.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 14.3%
White	22 78.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 10.7%
Not Hispanic or Latino	24 85.7%
Unknown or Not Reported	1 3.6%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Disease-Free Survival (DFS)
Description	1-year post-transplant disease free survival (DFS), defined as success if a patient is alive and disease free at 1-year post-transplant.
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TJU 2 Step Regimen
Arm/Group Description	All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone. Total Body Irradiation (TBI): Total body irradiation given in 8 fractions over 4 days (total dose of 12 Gy). Donor Lymphocyte Infusion (DLI): After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days. Cyclophosphamide: Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days Mycophenolate Mofetil (MMF): Started the day before the transplant to prevent graft versus host disease (GVHD) Tacrolimus: Started the day before the transplant to prevent graft-versus-host disease (GVHD) Hematopoietic stem cell transplantation (HSCT): One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-do
Measure Participants	28
Number [percentage of patients]	78.6

2. Primary Outcome

Title	Probability of Overall Survival at 15 Months Post-treatment
Description	Probability of overall survival at 15 months post-treatment, defined as success if a patient is alive 1-year post-transplant.
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TJU 2 Step Regimen
Arm/Group Description	All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone. Total Body Irradiation (TBI): Total body irradiation given in 8 fractions over 4 days (total dose of 12 Gy). Donor Lymphocyte Infusion (DLI): After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days. Cyclophosphamide: Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days Mycophenolate Mofetil (MMF): Started the day before the transplant to prevent graft versus host disease (GVHD) Tacrolimus: Started the day before the transplant to prevent graft-versus-host disease (GVHD) Hematopoietic stem cell transplantation (HSCT): One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-do
Measure Participants	28
Number [percentage of probability]	85

Adverse Events

Arm/Group Title	TJU 2 Step Regimen
Arm/Group Description	All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone. Total Body Irradiation (TBI): Total body irradiation given in 8 fractions over 4 days (total dose of 12 Gy). Donor Lymphocyte Infusion (DLI): After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days. Cyclophosphamide: Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days Mycophenolate Mofetil (MMF): Started the day before the transplant to prevent graft versus host disease (GVHD) Tacrolimus: Started the day before the transplant to prevent graft-versus-host disease (GVHD) Hematopoietic stem cell transplantation (HSCT): One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-do
All Cause Mortality
	TJU 2 Step Regimen
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TJU 2 Step Regimen
	Affected / at Risk (%)	# Events
Total	19/28 (67.9%)
Blood and lymphatic system disorders
HHV-6 infection	2/28 (7.1%)	2
Sepsis	1/28 (3.6%)	1
Gastrointestinal disorders
Diarrhea	3/28 (10.7%)	3
Colitis	1/28 (3.6%)	1
Cholecystitis	1/28 (3.6%)	1
General disorders
Infection	2/28 (7.1%)	2
Fever	8/28 (28.6%)	10
Headache	1/28 (3.6%)	1
BK cystitis	1/28 (3.6%)	1
Nausea	1/28 (3.6%)	1
Hypoxia	2/28 (7.1%)	2
Acute infusion reaction	1/28 (3.6%)	1
Immune system disorders
CMV reactivation	4/28 (14.3%)	4
Musculoskeletal and connective tissue disorders
Bone marrow cellularity	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Sinusitis	1/28 (3.6%)	1
Skin and subcutaneous tissue disorders
Subdural hematoma	1/28 (3.6%)	1
Brain injury from subdural hematoma	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	TJU 2 Step Regimen
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
Hypertension	12/28 (42.9%)	16
Hyperbilirubinemia	7/28 (25%)	9
Hypotension	19/28 (67.9%)	28
Hypokalemia	3/28 (10.7%)	4
Fluid overload	7/28 (25%)	8
Increased creatinine	7/28 (25%)	10
Pericather thrombus	3/28 (10.7%)	3
Hypernatremia	1/28 (3.6%)	1
Internal jugular thrombus	1/28 (3.6%)	1
Orthostatic hypotension	2/28 (7.1%)	2
Hyperglycemia	2/28 (7.1%)	2
Hypoglycemia	1/28 (3.6%)	1
HHV-6 reactivation	2/28 (7.1%)	2
Hypomagnesemia	1/28 (3.6%)	1
Electrolyte imbalance	9/28 (32.1%)	9
Platelet infusion reaction	1/28 (3.6%)	1
Elevated ferritin	1/28 (3.6%)	1
Hypercholesterolemia	1/28 (3.6%)	1
Hyperlipidemia	2/28 (7.1%)	2
Cardiac disorders
Tachycardia	20/28 (71.4%)	35
Palpitations	1/28 (3.6%)	1
Atrial fibrillation	2/28 (7.1%)	2
Ventricular systolic dysfunction	3/28 (10.7%)	3
Pericardial effusion	6/28 (21.4%)	6
Bradycardia	2/28 (7.1%)	3
Volume overload	1/28 (3.6%)	1
Ear and labyrinth disorders
Hearing problems	1/28 (3.6%)	1
Ringing in ears	1/28 (3.6%)	1
Eye disorders
Vision - flashing lights	1/28 (3.6%)	1
Blurry vision	4/28 (14.3%)	4
Visual acuity change/weakness	3/28 (10.7%)	3
Dry eyes	3/28 (10.7%)	3
Retinal hemorrhage	2/28 (7.1%)	2
Photophobia	3/28 (10.7%)	3
Tearing of eyes	1/28 (3.6%)	1
Blindness	1/28 (3.6%)	1
Gastrointestinal disorders
Rectal pain	2/28 (7.1%)	2
Epigastric pain/heartburn	9/28 (32.1%)	11
Diarrhea	25/28 (89.3%)	58
Constipation	13/28 (46.4%)	19
Mucositis	24/28 (85.7%)	24
Gastroesophageal reflux disease	7/28 (25%)	7
Clostridium difficile	6/28 (21.4%)	8
Hemorrhoids	3/28 (10.7%)	3
Gastroparesis pain	1/28 (3.6%)	1
Indigestion	1/28 (3.6%)	1
Neutropenic colitis	1/28 (3.6%)	1
Flatulence	3/28 (10.7%)	3
General disorders
Headache	18/28 (64.3%)	30
Decreased appetite	7/28 (25%)	7
Rigors	7/28 (25%)	8
Malaise	2/28 (7.1%)	2
Oral discomfort	1/28 (3.6%)	1
Sore throat	3/28 (10.7%)	3
Fatigue	26/28 (92.9%)	27
Back pain	13/28 (46.4%)	16
Insomnia	18/28 (64.3%)	21
Dry mouth	11/28 (39.3%)	12
Dysphagia	3/28 (10.7%)	3
Odynophagia	1/28 (3.6%)	1
Alopecia	1/28 (3.6%)	1
Clubbing of extremities	1/28 (3.6%)	1
Gum pain at site of tooth extraction	1/28 (3.6%)	1
Itching	10/28 (35.7%)	12
Cheek pain	1/28 (3.6%)	1
Jaw pain	3/28 (10.7%)	3
Nausea	11/28 (39.3%)	13
Leg pain	6/28 (21.4%)	6
Swollen eyelid	1/28 (3.6%)	1
Hand pain	2/28 (7.1%)	2
Abdominal pain	17/28 (60.7%)	25
Cold-like symptoms	2/28 (7.1%)	2
Vomiting	2/28 (7.1%)	3
Plaque on tongue	1/28 (3.6%)	1
Fever	24/28 (85.7%)	58
Vasovagal syncope	2/28 (7.1%)	2
Dizziness/lightheaded	12/28 (42.9%)	16
Tremors	6/28 (21.4%)	6
General pain	3/28 (10.7%)	3
Pain at PICC site	2/28 (7.1%)	2
Anorexia	8/28 (28.6%)	8
Sweats	3/28 (10.7%)	3
Night sweats	1/28 (3.6%)	1
Chills	8/28 (28.6%)	11
Abdominal cramps	3/28 (10.7%)	3
Cytomegalovirus reactivation	5/28 (17.9%)	5
Hip pain	4/28 (14.3%)	4
Muscle pain	8/28 (28.6%)	8
Puffy face	1/28 (3.6%)	1
Hyponatremia	5/28 (17.9%)	6
Leg cramping	1/28 (3.6%)	1
Head cold	1/28 (3.6%)	1
Muscle weakness	1/28 (3.6%)	1
Knee pain	3/28 (10.7%)	3
Groin pain	1/28 (3.6%)	1
Heel/ankle pain	2/28 (7.1%)	2
Trouble sleeping	7/28 (25%)	9
Lethargic	11/28 (39.3%)	11
Hypoxia	6/28 (21.4%)	9
Mouth ulceration	1/28 (3.6%)	1
Nose dryness	1/28 (3.6%)	1
Hiccups	3/28 (10.7%)	3
Ear pain	4/28 (14.3%)	4
Shoulder pain	4/28 (14.3%)	4
Eye pain	1/28 (3.6%)	1
Bloated feeling	2/28 (7.1%)	2
Arm swelling	4/28 (14.3%)	4
Neck pain	2/28 (7.1%)	3
Enlarged lymph node	1/28 (3.6%)	1
Chest pain	8/28 (28.6%)	10
Neck stiffness	3/28 (10.7%)	6
Swollen face	1/28 (3.6%)	1
Pain at lung biopsy site	1/28 (3.6%)	1
Difficulty walking	1/28 (3.6%)	1
Feet pain	3/28 (10.7%)	3
Malnutrition	1/28 (3.6%)	1
Weight loss	1/28 (3.6%)	1
Hot flashes	1/28 (3.6%)	1
Arm pain	3/28 (10.7%)	5
Swollen ankles	1/28 (3.6%)	1
Dehydration	2/28 (7.1%)	2
Bone pain	2/28 (7.1%)	3
Penile/scrotum pain	1/28 (3.6%)	1
Tongue lumps	1/28 (3.6%)	1
Altered taste	1/28 (3.6%)	1
Parotitis	1/28 (3.6%)	1
Difficulty concentrating	1/28 (3.6%)	1
Visual disturbance	1/28 (3.6%)	1
Shin pain	1/28 (3.6%)	1
Low TSH	1/28 (3.6%)	1
Hepatobiliary disorders
Increased LFTs	4/28 (14.3%)	6
Infections and infestations
Meningitis	1/28 (3.6%)	1
Thrush	2/28 (7.1%)	2
Musculoskeletal and connective tissue disorders
Knee - decreased range of motion	1/28 (3.6%)	1
Muscle spasms	1/28 (3.6%)	1
Opisthotonus	1/28 (3.6%)	1
Joint aches	1/28 (3.6%)	1
Nervous system disorders
Parasthesia of foot	2/28 (7.1%)	2
Numbness/tingling	5/28 (17.9%)	5
Neuropathy	7/28 (25%)	7
Seizures	1/28 (3.6%)	2
Paresthesia	1/28 (3.6%)	1
Sensitivity to hot/cold	1/28 (3.6%)	1
Psychiatric disorders
Anxiety	19/28 (67.9%)	22
Hallucinations	2/28 (7.1%)	2
Decreased sense of well-being	1/28 (3.6%)	1
Depression	7/28 (25%)	7
Mild distress	1/28 (3.6%)	1
Frustration	1/28 (3.6%)	1
Agitation	2/28 (7.1%)	3
Altered mental status	2/28 (7.1%)	2
Speech or memory change	1/28 (3.6%)	1
Auditory hallucinations	1/28 (3.6%)	1
Discouraged	1/28 (3.6%)	1
Nightmares	1/28 (3.6%)	1
Renal and urinary disorders
Dysuria	10/28 (35.7%)	13
Urinary frequency	2/28 (7.1%)	2
Perinephric fluid	1/28 (3.6%)	1
Nocturia	9/28 (32.1%)	9
Decreased urine output	7/28 (25%)	8
BK viremia	1/28 (3.6%)	1
Hematuria	2/28 (7.1%)	2
Urinary incontinence	3/28 (10.7%)	3
Orange urine	1/28 (3.6%)	1
Polyuria	1/28 (3.6%)	1
Urinary retention	1/28 (3.6%)	1
Reproductive system and breast disorders
Vagina - whitish coating	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	10/28 (35.7%)	10
Congestion	11/28 (39.3%)	14
Rhinorrhea	3/28 (10.7%)	3
Dyspnea	15/28 (53.6%)	23
Upper respiratory infection	2/28 (7.1%)	2
Diminished breath sounds	1/28 (3.6%)	1
Wheezing	2/28 (7.1%)	2
Dry cough	2/28 (7.1%)	2
Tachypnea	4/28 (14.3%)	6
Pleural effusion	2/28 (7.1%)	2
Aspiration	1/28 (3.6%)	1
Allergic rhinitis	1/28 (3.6%)	1
Pulmonary infiltrates	1/28 (3.6%)	1
Pneumonitis	1/28 (3.6%)	1
Skin and subcutaneous tissue disorders
Rash	23/28 (82.1%)	52
Ulcer	1/28 (3.6%)	1
Tongue sores	1/28 (3.6%)	1
Erythema	2/28 (7.1%)	2
Flushing/erythema	2/28 (7.1%)	2
Dry skin	10/28 (35.7%)	12
Hyperpigmentation	2/28 (7.1%)	2
Mild desquamation on fingers	1/28 (3.6%)	1
Edema	4/28 (14.3%)	4
Papules	1/28 (3.6%)	1
Burning of soles of hands and feet	1/28 (3.6%)	1
Abdominal distension	1/28 (3.6%)	1
Penile lesion	1/28 (3.6%)	2
Blisters	1/28 (3.6%)	1
Hypopigmentation	1/28 (3.6%)	1
Skin irritation	1/28 (3.6%)	1
Hives	2/28 (7.1%)	2
Penile blister	1/28 (3.6%)	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.