A Two-Step Approach to Bone Marrow Transplant Using Cells From Two Partially-Matched Relatives

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01532635
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II clinical trial studies how well two donors stem cell transplant work in treating patients with high-risk hematologic malignancies. After receiving radiation to help further treat the disease, patients receive a dose of donors' T cells. T cells can fight infection and react against cancer cells. Two days after donors' T cells are given, patients receive cyclophosphamide (CY) to help destroy the most active T cells that may cause tissue damage (called graft versus host disease or GVHD). Some of the less reactive T cells are not destroyed by CY and they remain in the patient to help fight infection. A few days after the CY is given, patients receive donors' stem cells to help their blood counts recover. Using two donors' stem cell transplant instead of one donor may be more effective in treating patients with high-risk disease and may prevent the disease from coming back.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancy; Leukemia; Acute Lymphoblastic Leukemia; ALL; Acute Myelogenous Leukemia; AML; Chronic Lymphocytic Leukemia; CLL; Lymphoma; Hodgkin's Lymphoma; Non-hodgkin's Lymphoma; Myeloma	Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide (CY); Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF); Biological: Hematopoietic Stem Cell Transplant (HSCT)	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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 using 2 donors.

SECONDARY OBJECTIVES:

1. To assess the consistency and pace of engraftment. II. To assess the pace of T cell and B cell immune recovery in patients in each arm.

2. To assess regimen related toxicity, graft-versus-host disease (GVHD) incidence and severity, and overall survival.

3. To assess the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups.

4. To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment.

5. If dominance is observed, to compare the donors with regard to degree of human leukocyte antigen (HLA) mismatch, killer Ig-like receptor (KIR) types, cluster of differentiation (CD)34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, natural killer (NK) cell, or other cellular subsets prior to emerging in the graft as a whole.

6. To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate.

7. 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. When observed, to correlate loss of one HLA haplotype with: a) receipt of a transplant capable of targeting only that haplotype; b) establishment of dominance in a 2 haplotype transplant such that the lost haplotype would be the primary target of the dominant donor; c) being the target of the donor predicted to be more alloreactive in a 2 haplotype transplant.

OUTLINE:

CONDITIONING: Patients undergo total-body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.

After completion of study treatment, patients are followed up for 1 year, and then periodically thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 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 Two Related Donors
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Allogeneic HSCT Using Two Related Donors CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.

Radiation: Total Body Irradiation (TBI); TBI twice daily for 4 days and occurs 6 to 9 days prior to the transplant. Total radiation dose is 12 Gy.; Other Names: TBI radiotherapy ; Biological: Donor Lymphocyte Infusion (DLI); DLI given 6 days prior to transplant (HSCT).; Other Names: DLI T cell infusion ; Drug: Cyclophosphamide (CY); Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).; Other Names: CY Endoxan Cytoxan Neosar Procytox Revimmune cytophosphane ; Drug: Tacrolimus; Tacrolimus is started the day before the transplant and stops a few months after transplant.; Other Names: FK-506 fujimycin Prograf Advagraf Protopic ; Drug: Mycophenolate Mofetil (MMF); MMF is started the day before transplant and stops a few weeks after transplant.; Other Names: MMF CellCept Myfortic ; Biological: Hematopoietic Stem Cell Transplant (HSCT); CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed using donor cells from two related donors. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem cells.; Other Names: HSCT stem cell transplant CliniMACS

Outcome Measures

Primary Outcome Measures

1. One Year Relapse-Free Survival [1 year]

   To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover.

Secondary Outcome Measures

1. Chimerism Assessment [1 year]

   To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment.

2. Assessment of Dominance [1 year]

   If dominance is observed, to compare the 2 donors with regard to degree of HLA mismatch, KIR types, CD 34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, NK cell, or other cellular subsets prior to emerging in the graft as a whole.

3. Relapse Rates [1 year]

   To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate.

4. Engraftment [1 year]

   To assess the consistency and pace of engraftment of both donors.

5. Immune Reconstitution [1 year]

   Assess T and B cell Reconstitution

6. Non-relapse Morbidity and Mortality [1 year]

   Assessment of regimen related toxicity, GVHD incidence and severity, and overall survival.

7. Tolerance of DLI [2-6 days prior to transplant]

   Assessment of the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups

8. Assessment for Tumor Escape Mechanisms [1 year post transplant]

   To test for loss of one or both HLA haplotypes in patients who relapse post-transplant and examine the relapse in the context of the characteristics of the 2 donors

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

2. Patients must have two related donors that meet an acceptable scenario as described above.

3. Patients must adequate organ function:

• LVEF of >= 50%

• DLCO (adjusted for hemoglobin) >= 50% of predicted

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

• Creatinine clearance of >= 60 ml/min

1. Karnofsky Performance Status of > 80 % on the modified KPS tool (see Appendix A).

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

3. Able to give informed consent

Exclusion Criteria:

1. Modified KPS of < 80%

2. = 5 Comorbidity Points on the HCT-CI Index (See Appendix B)

3. 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. ATG level of >= 2 ugm/ml

11. Patients with active inflammatory processes (such as flair of an autoimmune disease) including T max > 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	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: NCT01532635
• Other Study ID Numbers: 11D.570; 2011-101
• First Posted: Feb 14, 2012
• Last Update Posted: Nov 29, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Sidney Kimmel Cancer Center at Thomas Jefferson University: hematologic malignancy; leukemia; Acute lymphoblastic leukemia; ALL; Acute myelogenous leukemia; AML; Chronic lymphocytic leukemia; CLL; lymphoma; hodgkin's lymphoma; non-hodgkin's lymphoma; myeloma; allogeneic stem cell transplant; TJU 2-step; Hematopoietic stem cell transplant; HSCT; bone marrow transplant; Cyclophosphamide; MMF; Mycophenolate Mofetil
• Additional relevant MeSH terms: Lymphoma; Leukemia; Neoplasms; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Mycophenolic Acid; Cyclophosphamide; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Overall Participants	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.35 (20.64)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
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	0 0%
White	4 100%
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	4 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	One Year Relapse-Free Survival
Description	To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

2. Secondary Outcome

Title	Chimerism Assessment
Description	To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

3. Secondary Outcome

Title	Assessment of Dominance
Description	If dominance is observed, to compare the 2 donors with regard to degree of HLA mismatch, KIR types, CD 34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, NK cell, or other cellular subsets prior to emerging in the graft as a whole.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

4. Secondary Outcome

Title	Relapse Rates
Description	To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

5. Secondary Outcome

Title	Engraftment
Description	To assess the consistency and pace of engraftment of both donors.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

6. Secondary Outcome

Title	Immune Reconstitution
Description	Assess T and B cell Reconstitution
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

7. Secondary Outcome

Title	Non-relapse Morbidity and Mortality
Description	Assessment of regimen related toxicity, GVHD incidence and severity, and overall survival.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

8. Secondary Outcome

Title	Tolerance of DLI
Description	Assessment of the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups
Time Frame	2-6 days prior to transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

9. Secondary Outcome

Title	Assessment for Tumor Escape Mechanisms
Description	To test for loss of one or both HLA haplotypes in patients who relapse post-transplant and examine the relapse in the context of the characteristics of the 2 donors
Time Frame	1 year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Measure Participants	0

Adverse Events

Arm/Group Title	Allogeneic HSCT Using Two Related Donors
Arm/Group Description	CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
All Cause Mortality
	Allogeneic HSCT Using Two Related Donors
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Allogeneic HSCT Using Two Related Donors
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Blood and lymphatic system disorders
Hyperbilirubinemia	1/4 (25%)	1
Hypoxia	1/4 (25%)	1
Cardiac disorders
Left ventricular systolic dysfunction	1/4 (25%)	1
Pericardial effusion	1/4 (25%)	1
General disorders
Fevers	1/4 (25%)	1
Dehydration	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/4 (25%)	1
Pulmonary edema	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Allogeneic HSCT Using Two Related Donors
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Bacteremia	1/4 (25%)	1
Electrolyte imbalance	3/4 (75%)	3
Fluid overload	2/4 (50%)	3
HHV-6 reactivation	1/4 (25%)	1
Hyperbilirubinemia	4/4 (100%)	6
Hypertension	2/4 (50%)	3
Hypokalemia	1/4 (25%)	2
Hyponatremia	1/4 (25%)	1
Hypotension	3/4 (75%)	5
Hypoxia	2/4 (50%)	3
Increased creatinine	3/4 (75%)	4
Orthostatic hypotension	2/4 (50%)	2
Platelet transfusion reaction	1/4 (25%)	1
Cardiac disorders
Atrial fibrillation	1/4 (25%)	1
Tachycardia	2/4 (50%)	3
Volume overload	1/4 (25%)	1
Eye disorders
Change in vision	1/4 (25%)	1
Gastrointestinal disorders
Clostridium difficile	1/4 (25%)	1
Constipation	2/4 (50%)	4
Diarrhea	4/4 (100%)	9
Dyspepsea	1/4 (25%)	1
Heartburn	2/4 (50%)	2
Mucositis	4/4 (100%)	4
General disorders
Abdominal pain	2/4 (50%)	4
Arm pain	1/4 (25%)	1
Back pain	2/4 (50%)	2
Balance problems	1/4 (25%)	1
Chest pain	3/4 (75%)	4
Chest tightness	1/4 (25%)	1
Chills	2/4 (50%)	2
Dehydration	1/4 (25%)	1
Dizziness	1/4 (25%)	1
Dry eyes	1/4 (25%)	1
Fatigue	2/4 (50%)	2
Feet pain	1/4 (25%)	1
Fevers	4/4 (100%)	11
Generalized pain	2/4 (50%)	2
Generalized weakness	1/4 (25%)	1
Hand pain	1/4 (25%)	1
Headache	3/4 (75%)	3
Hiccups	1/4 (25%)	1
Hypothermia	1/4 (25%)	1
Increased alkaline phosphatase	1/4 (25%)	1
Knee pain	1/4 (25%)	1
Leg pain	1/4 (25%)	1
Neck pain	1/4 (25%)	1
Parotitis	1/4 (25%)	1
Rectal pain	1/4 (25%)	1
Rigors	1/4 (25%)	1
Shoulder pain	1/4 (25%)	1
Swollen ankles	1/4 (25%)	1
Toenail bleeding	1/4 (25%)	1
Trouble sleeping	2/4 (50%)	2
Upper extremity swelling	1/4 (25%)	1
Vaginal discomfort/itching	1/4 (25%)	1
Weight loss	1/4 (25%)	1
Hepatobiliary disorders
Increased LFTs	1/4 (25%)	1
Immune system disorders
CMV reactivation	2/4 (50%)	2
Metabolism and nutrition disorders
Malnutrition	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Osteopenia	1/4 (25%)	1
Psychiatric disorders
Anxiety	2/4 (50%)	2
Depression	1/4 (25%)	1
Mental status change	1/4 (25%)	1
Renal and urinary disorders
Decreased urine output	2/4 (50%)	4
Dysuria	2/4 (50%)	4
Hematuria	2/4 (50%)	2
Nocturia	2/4 (50%)	2
Urinary retention	2/4 (50%)	2
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/4 (25%)	1
Dyspnea	2/4 (50%)	2
Pneumonitis	2/4 (50%)	2
Tachypnea	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Edema	1/4 (25%)	1
GVHD rash	1/4 (25%)	1
Pruritus	1/4 (25%)	1
Rash	4/4 (100%)	9

Limitations/Caveats

Study was terminated due to poor accrual. No reportable data has been collected.

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.