Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01273766
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arms: 3
• Duration (Months): 47
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Deferasirox may remove excess iron from the body caused by blood transfusions.

PURPOSE: This clinical trial studies deferasirox in treating iron overload caused by blood transfusions in patients with hematologic malignancies.

Condition or Disease	Intervention/Treatment	Phase
Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Langerhans Cell Histiocytosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Mast Cell Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelofibrosis; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Waldenstrom Macroglobulinemia	Drug: deferasirox; Other: laboratory biomarker analysis; Other: enzyme-linked immunosorbent assay	Phase 2

Detailed Description

PRIMARY OBJECTIVES: I. To determine the effects of the iron-chelating agent deferasirox on changes in: neutrophil function; macrophage function; lymphocyte function.

SECONDARY OBJECTIVES: I. To determine the effect of chelation on the incidence of bacterial, viral and fungal infections documented by clinical, microbiologically-proven versus radiologically-proven criteria. II. To determine the effect of iron chelation on mortality and morbidity with incidence of the following parameters: Need for hospitalization; Duration of hospitalization; Need for ventilatory support; Need for exchange transfusion/apheresis; Need for treatment with antifungals or antibiotics for documented infections.

OUTLINE: Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Impact of Intervention With Deferasirox on the Immune Function of Patients With Hematologic Diseases and Transfusion-Related Iron Overload
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity.	Drug: deferasirox; Given orally; Other Names: Exjade ICL670 ; Other: laboratory biomarker analysis; Correlative studies; Other: enzyme-linked immunosorbent assay; Correlative studies; Other Names: ELISA
No Intervention: control arm blood tested on healthy patients
No Intervention: correlative treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis

Outcome Measures

Primary Outcome Measures

1. Changes in Mean Neutrophil Values (as Measured by Lab) for Arm 1 (Other Arms Were Used for Calibration Only) [Baseline, up to 6 months]

   Changes in Neutrophils between baseline and mean neutrophils values during treatment (measured after each dose)

Secondary Outcome Measures

1. Need for Hospitalization, Ventilator Support, Exchange Transfusion/Apheresis or Treatment With Antifungals or Antibiotics [Baseline, up to 6 months]

   Records will be assessed at baseline and prospectively while on study.

2. Cumulative Incidence of Documented Bacterial, Fungal, and Viral Infections [Baseline, up to 6 months]

   Records will be assessed at baseline and prospectively while on study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have a pathology confirmed diagnosis of one of the following: myelodysplastic syndrome (MDS); acute leukemia; multiple myeloma; myelofibrosis; lymphoma; chronic anemia; sickle cell anemia

• Iron score >= 2

• Absolute Neutrophil Count (ANC) >= 1,000

• Platelets >= 50,000

• Albumin >= 2 g/dL

• Alkaline phosphatase =< 5X Upper Limit of Normal (ULN)

• Total bilirubin =< 1.5

• Creatinine =< 2X age-appropriate Upper Limit of Normal (ULN) OR creatinine clearance

= 40 ml/min

• Serum Glutamic Oxaloacetic Transaminase (SGOT) [AST] and Serum Glutamic Pyruvic Transaminase (SGPT) [ALT] =< 5X Upper Limit of Normal (ULN)

• Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients with active disease undergoing chemotherapy treatment

• Patient who have been treated with rituximab or immunomodulating drugs =< 1 month prior to enrollment

• HIV-positive patients

• Hepatitis-C positive patients

• Women who are pregnant or breastfeeding

• Patients on hemodialysis/patients with renal failure

• Patients with sepsis or acute illness

• Known hypersensitivity to deferasirox

• Patients with moderate or severe hearing loss as defined by audiogram

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center of Wake Forest University	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mary Ann Knovich, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01273766
• Other Study ID Numbers: IRB00015287; NCI-2010-02228; CCCWFU 97710
• First Posted: Jan 10, 2011
• Last Update Posted: Sep 7, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Preleukemia; Lymphoma, Non-Hodgkin; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Sezary Syndrome; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Leukemia-Lymphoma, Adult T-Cell; Waldenstrom Macroglobulinemia; Lymphoma, Large-Cell, Anaplastic; Lymphomatoid Granulomatosis; Lymphoma, Extranodal NK-T-Cell; Intraocular Lymphoma; Leukemia, Mast-Cell; Histiocytosis, Langerhans-Cell; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Anemia, Refractory; Immunoblastic Lymphadenopathy; Myelodysplastic-Myeloproliferative Diseases; Histiocytosis; Iron Overload; Syndrome; Recurrence; Deferasirox

Study Results

Participant Flow

Arm/Group Title	Arm I	Control Arm	Correlative
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies	blood tested on healthy patients	treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
Period Title: Overall Study
STARTED	4	7	5
COMPLETED	4	7	5
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Arm I	Control Arm	Correlative	Total
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies	blood tested on healthy patients	treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis	Total of all reporting groups
Overall Participants	4	7	5	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 75%	7 100%	4 80%	14 87.5%
>=65 years	1 25%	0 0%	1 20%	2 12.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.1 (12.9)	40.1 (7.0)	55.0 (17.6)	48.0 (14.5)
Sex: Female, Male (Count of Participants)
Female	2 50%	6 85.7%	1 20%	9 56.3%
Male	2 50%	1 14.3%	4 80%	7 43.8%
Region of Enrollment (participants) [Number]
United States	4 100%	7 100%	5 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Mean Neutrophil Values (as Measured by Lab) for Arm 1 (Other Arms Were Used for Calibration Only)
Description	Changes in Neutrophils between baseline and mean neutrophils values during treatment (measured after each dose)
Time Frame	Baseline, up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies
Measure Participants	4
Mean (Standard Deviation) [10^9 Neutrophils per Liter]	7.8 (138.4)

2. Secondary Outcome

Title	Need for Hospitalization, Ventilator Support, Exchange Transfusion/Apheresis or Treatment With Antifungals or Antibiotics
Description	Records will be assessed at baseline and prospectively while on study.
Time Frame	Baseline, up to 6 months

Outcome Measure Data

Analysis Population Description

Number analyzed in rows differs from overall because data was not collected on all participants.

Arm/Group Title	Arm I	Correlative
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies	treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
Measure Participants	4	5
Baseline : Hospitalization	2 50%	5 71.4%
Baseline : Ventilator	0 0%	1 14.3%
Baseline : Transfusion	0 0%	0 0%
Baseline : Antibiotics	0 0%	5 71.4%
1 Month : Hospitalization	1 25%	1 14.3%
1 Month : Ventilator	0 0%	0 0%
1 Month : Transfusion	0 0%	1 14.3%
1 Month : Antibiotics	1 25%	1 14.3%
2 Month : Hospitalization	0 0%	1 14.3%
2 Month : Ventilator	0 0%	0 0%
2 Month : Transfusion	0 0%	1 14.3%
2 Month : Antibiotics	0 0%	1 14.3%
3 Month : Hospitalization	0 0%	1 14.3%
3 Month : Ventilator	0 0%	0 0%
3 Month : Transfusion	0 0%	1 14.3%
3 Month : Antibiotics	0 0%	0 0%
4 Month : Hospitalization	0 0%	1 14.3%
4 Month : Ventilator	0 0%	1 14.3%
4 Month : Transfusion	0 0%	1 14.3%
4 Month : Antibiotics	1 25%	1 14.3%
5 Month : Hospitalization	0 0%	2 28.6%
5 Month : Ventilator	0 0%	0 0%
5 Month : Transfusion	0 0%	0 0%
5 Month : Antibiotics	0 0%	1 14.3%
6 Month : Hospitalization	3 75%	0 0%
6 Month : Ventilator	0 0%	0 0%
6 Month : Transfusion	0 0%	0 0%
6 Month : Antibiotics	1 25%	0 0%

3. Secondary Outcome

Title	Cumulative Incidence of Documented Bacterial, Fungal, and Viral Infections
Description	Records will be assessed at baseline and prospectively while on study.
Time Frame	Baseline, up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Correlative
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies	treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
Measure Participants	4	5
Count of Participants [Participants]	2 50%	5 71.4%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	only patients on Arm I (recieving drug on protocol) were tracked for toxicities
Arm/Group Title	Arm I		Control Arm		Correlative
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies		blood tested on healthy patients		treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
All Cause Mortality
	Arm I		Control Arm		Correlative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I		Control Arm		Correlative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		0/0 (NaN)		0/0 (NaN)
General disorders
Fatigue	2/4 (50%)	3	0/0 (NaN)	0	0/0 (NaN)	0
Heartburn/dyspepsia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Confusion	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
"Distension bloating, abdominal"	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Infections and infestations
Infection Bladder	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Cystitis	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Lung infection	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Infection Sinus	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Injury, poisoning and procedural complications
Infection with normal ANC or Grade 1 or 2 neutrophils: Nose	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Investigations
hyperglycemia	2/4 (50%)	6	0/0 (NaN)	0	0/0 (NaN)	0
hyponatremia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
hypokalemia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
serum glutamic pyruvic transaminase	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Lipase	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Lymphopenia	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Vascular disorders
Thrombosis/thrombus/embolism	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Arm I		Control Arm		Correlative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		0/0 (NaN)		0/0 (NaN)
Eye disorders
Ocular/Visual - Other	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Dry eye syndrome	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
blurred vision	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Gastrointestinal disorders
Nausea	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Vomiting	1/4 (25%)	3	0/0 (NaN)	0	0/0 (NaN)	0
Constipation	2/4 (50%)	4	0/0 (NaN)	0	0/0 (NaN)	0
General disorders
Anorexia	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Gastrointestinal - Other	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Taste alteration	1/4 (25%)	5	0/0 (NaN)	0	0/0 (NaN)	0
Insomnia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Fatigue	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Weight loss	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Pain: Head/headache	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Urinary frequency/urgency	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Renal/Genitourinary - Other	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Intra-operative Injury	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Musculoskeletal Soft Tissue - Other	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Dry mouth	3/4 (75%)	3	0/0 (NaN)	0	0/0 (NaN)	0
Dehydration	2/4 (50%)	3	0/0 (NaN)	0	0/0 (NaN)	0
Pruritus/itching	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Pain: Abdomen	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Ataxia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Obstruction Bladder	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Pain Bladder	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Urine color change	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Anal Incontinence	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Memory impairment	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Pain: Muscle	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Pain Oral cavity	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Pain: Extremity-limb	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Hyperpigmentation	1/4 (25%)	5	0/0 (NaN)	0	0/0 (NaN)	0
Infections and infestations
Lung infection	2/4 (50%)	3	0/0 (NaN)	0	0/0 (NaN)	0
Mucositis/stomatitis Oral cavity	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Mucositis/stomatitis Oral cavity	3/4 (75%)	11	0/0 (NaN)	0	0/0 (NaN)	0
Infection Lip perioral	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Blood Infection with high grade neutropenia	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Investigations
Low WBC	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
low Platelets	3/4 (75%)	9	0/0 (NaN)	0	0/0 (NaN)	0
Low Hemoglobin	4/4 (100%)	15	0/0 (NaN)	0	0/0 (NaN)	0
Alkaline phosphatase	3/4 (75%)	10	0/0 (NaN)	0	0/0 (NaN)	0
Creatinine	2/4 (50%)	7	0/0 (NaN)	0	0/0 (NaN)	0
Proteinuria	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0
hyperglycemia	4/4 (100%)	15	0/0 (NaN)	0	0/0 (NaN)	0
hypoglycemia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
hypocalcemia	4/4 (100%)	4	0/0 (NaN)	0	0/0 (NaN)	0
hypomagnesemia	3/4 (75%)	3	0/0 (NaN)	0	0/0 (NaN)	0
hyponatremia	3/4 (75%)	7	0/0 (NaN)	0	0/0 (NaN)	0
hypokalemia	1/4 (25%)	3	0/0 (NaN)	0	0/0 (NaN)	0
hypoalbuminemia	4/4 (100%)	6	0/0 (NaN)	0	0/0 (NaN)	0
hyperbilirubinemia	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
serum glutamic pyruvic transaminase	2/4 (50%)	10	0/0 (NaN)	0	0/0 (NaN)	0
serum glutamic oxaloacetic transaminase	1/4 (25%)	6	0/0 (NaN)	0	0/0 (NaN)	0
hypermagnesemia	2/4 (50%)	4	0/0 (NaN)	0	0/0 (NaN)	0
hyperkalemia	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Amylase	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
gamma-Glutamyl transpeptidase	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Glomerular filtration rate	2/4 (50%)	4	0/0 (NaN)	0	0/0 (NaN)	0
Lipase	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Lymphopenia	2/4 (50%)	4	0/0 (NaN)	0	0/0 (NaN)	0
Nervous system disorders
Tremor	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Cough	2/4 (50%)	3	0/0 (NaN)	0	0/0 (NaN)	0
Bronchospasm wheezing	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Skin and subcutaneous tissue disorders
Dermatology/Skin	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Rash/desquamation	2/4 (50%)	5	0/0 (NaN)	0	0/0 (NaN)	0
Allergic rhinitis	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Vascular disorders
Hemorrhage GU: Urinary	1/4 (25%)	2	0/0 (NaN)	0	0/0 (NaN)	0
Thrombosis/embolism (vascular access-related)	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0

Limitations/Caveats

adverse events were only tracked on Arm I

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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.