Vyxeos(CPX-351) in Adults w R/R Acute Lymphoblastic Leukemia

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03575325
• Collaborator: Jazz Pharmaceuticals (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 49.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study involves Vyxeos (CPX-351), a formulation of a fixed combination of the two anti-tumor drugs, cytarabine and daunorubicin that will be given as an infusion over 90 minutes. This study will use what is called a "liposome" injection. This is a special fat capsule (called a liposome) that surrounds the cytarabine and daunorubicin and protects the drugs from being eliminated/destroyed by the body.

Condition or Disease	Intervention/Treatment	Phase
Lymphoid Leukemia; Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia; Relapsed Acute Lymphoblastic Leukemia	Drug: CPX-351	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is an open label, single arm, single center, phase 2 pilot study of Vyxeos induction & consolidation in relapsed and refractory ALL.This is an open label, single arm, single center, phase 2 pilot study of Vyxeos induction & consolidation in relapsed and refractory ALL.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Open-Label Phase 2 Pilot Study of Vyxeos (CPX-351) in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia
• Actual Study Start Date: Oct 11, 2018
• Actual Primary Completion Date: Jun 7, 2021
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CPX-351 Treatment Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles).	Drug: CPX-351; The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.; Other Names: Vyxeos cytarabine:daunorubicin

Outcome Measures

Primary Outcome Measures

1. Complete Remission Rate (CR) + CR With Incomplete Recovery (CRi) [At day 28]

   Expansion from phase II pilot to a phase II trial will depend on demonstration of CR/CRi amongst 4 of the initial 10 treated patients. Investigators will measure remission rate at day 28 to address the primary endpoint of complete remission (with or without complete hematologic recovery), as defined by Cheson Criteria (ref 27). For those with extramedullary disease, Lugano criteria will be used to assess response. This is a standard assessment of drug efficacy for phase 2 clinical trial design in acute leukemias, as response correlates closely with progression free- and overall survival (PFS and OS).

Secondary Outcome Measures

1. Progression Free Survival (PFS) [12 months]

   Progression Free Survival as defined by Cheson and Lugano Criteria, namely progression, failure to respond, or death, as assessed from time of first treatment. Progression Free Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment.

2. Overall Survival (OS) [12 months]

   Overall Survival as defined by Cheson and Lygano Criteria, namely death due to any cause as assessed from time of first treatment. Overall Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment.

3. Minimal Residual Disease (MRD) [At day 28]

   MRD assessment will be provided using ClonoSeq test result. ClonoSEQ® is an FDA-cleared test used to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Willing and able to provide written informed consent/assent for the trial.

• Be ≥ 18 years of age on day of signing informed consent.

• Able to adhere to the study visit schedule and other protocol requirements.

• Pathologically confirmed B- or T-cell acute lymphoblastic or mixed phenotype acute leukemia, with >5% peripheral blood or bone marrow lymphoblasts and/or extramedullary disease >1x1cm.

• Relapsed or refractory acute lymphoblastic leukemia after at least 1 prior cycle of therapy. Patients with Philadelphia chromosome positive disease must have failed at least two prior tyrosine kinase inhibitors.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• Cardiac ejection fraction ≥ 50% by echocardiography or multigated acquisition scan (MUGA).

• Must be at least 2 weeks out from any prior systemic chemotherapy, blinatumumab, radiation, and/or other investigational agents, and have recovered to grade 1 from any toxicity related to prior therapy. Glucocorticoids are permitted up to 1 day prior to the first dose.

• Serum bilirubin and creatinine less than 1.5x upper limit of normal (ULN). AST and ALT must be less than 3x ULN, unless there is suspected liver involvement.

• Females of childbearing potential (FCBP) must have a negative serum pregnancy test at screening. A FCBP is considered when a sexually mature female: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months.

• A FCBP must agree to use of two methods of highly effective contraception, be surgically sterile, or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study treatment.

• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 30 days after the last dose of study therapy. Men must agree to not donate sperm during and after the study

Exclusion Criteria:

• Clinical evidence of active central nervous system (CNS) leukemia.

• Any major surgery or radiation therapy within four weeks.

• Any active infection requiring systemic therapy, including HIV, Hepatitis B, and/or Hepatitis C.

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator (including but not limited to severe graft-versus-host disease, unstable angina, pulmonary hypertension, active/prior veno-occlusive disease of the liver or severe CHF (NYHA III-IV).

• Patients with active (uncontrolled, metastatic) second malignancies.

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 after the last dose of trial treatment.

• Hypersensitivity to cytarabine, daunorubicin, or liposomal products.

• History of Wilson's disease or other copper-metabolism disorder.

• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m^2 daunorubicin or equivalent).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Jazz Pharmaceuticals

Investigators

• Principal Investigator: Bijal Shah, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 11, 2019

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT03575325
• Other Study ID Numbers: MCC-19482
• First Posted: Jul 2, 2018
• Last Update Posted: Jul 29, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: T-cell acute lymphoblastic leukemia; B-cell acute lymphoblastic leukemia
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Cytarabine; Daunorubicin

Study Results

Participant Flow

Arm/Group Title	CPX-351 Treatment
Arm/Group Description	Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles). CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Period Title: Overall Study
STARTED	11
COMPLETED	10
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	CPX-351 Treatment
Arm/Group Description	Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles). CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 90.9%
>=65 years	1 9.1%
Sex: Female, Male (Count of Participants)
Female	2 18.2%
Male	9 81.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 27.3%
Not Hispanic or Latino	8 72.7%
Unknown or Not Reported	0 0%
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	4 36.4%
White	5 45.5%
More than one race	0 0%
Unknown or Not Reported	2 18.2%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Complete Remission Rate (CR) + CR With Incomplete Recovery (CRi)
Description	Expansion from phase II pilot to a phase II trial will depend on demonstration of CR/CRi amongst 4 of the initial 10 treated patients. Investigators will measure remission rate at day 28 to address the primary endpoint of complete remission (with or without complete hematologic recovery), as defined by Cheson Criteria (ref 27). For those with extramedullary disease, Lugano criteria will be used to assess response. This is a standard assessment of drug efficacy for phase 2 clinical trial design in acute leukemias, as response correlates closely with progression free- and overall survival (PFS and OS).
Time Frame	At day 28

Outcome Measure Data

Analysis Population Description

Evaluable participants

Arm/Group Title	CPX-351 Treatment
Arm/Group Description	Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles). CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Measure Participants	10
Number [Percent of participants]	30 272.7%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression Free Survival as defined by Cheson and Lugano Criteria, namely progression, failure to respond, or death, as assessed from time of first treatment. Progression Free Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable participants

Arm/Group Title	CPX-351 Treatment
Arm/Group Description	Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles). CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Measure Participants	10
Median (95% Confidence Interval) [Days]	57

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival as defined by Cheson and Lygano Criteria, namely death due to any cause as assessed from time of first treatment. Overall Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable participants

Arm/Group Title	CPX-351 Treatment
Arm/Group Description	Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles). CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Measure Participants	10
Median (95% Confidence Interval) [Days]	218

4. Secondary Outcome

Title	Minimal Residual Disease (MRD)
Description	MRD assessment will be provided using ClonoSeq test result. ClonoSEQ® is an FDA-cleared test used to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL).
Time Frame	At day 28

Outcome Measure Data

Analysis Population Description

Evaluable participants - Participants who achieved CR or CRi

Arm/Group Title	CPX-351 Treatment
Arm/Group Description	Participants will receive induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. This may be followed by consolidation with CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles). CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Measure Participants	3
No trackable clone by ClonoSeq	2 18.2%
Complete Molecular Remission by ClonoSeq	1 9.1%

Adverse Events

Time Frame	Adverse events were collected from the time of consent until 30 days after the last dose of CPX-351, approximately 34 months.
Arm/Group Title	CPX-351 Treatment Induction Dose		CPX-351 Treatment Induction Dose + 1 Consolidation Dose		CPX-351 Treatment +2 Consolidation Doses
Arm/Group Description	Participants who received induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle.		Participants who received induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. Participants then received one consolidation dose of CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle		Participants who received induction with CPX-351 at a dose of 100 u/m^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle. Participants then received two consolidation doses of CPX-351 at a dose of 65 u/m^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle
All Cause Mortality
	CPX-351 Treatment Induction Dose		CPX-351 Treatment Induction Dose + 1 Consolidation Dose		CPX-351 Treatment +2 Consolidation Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		0/3 (0%)		0/1 (0%)
Serious Adverse Events
	CPX-351 Treatment Induction Dose		CPX-351 Treatment Induction Dose + 1 Consolidation Dose		CPX-351 Treatment +2 Consolidation Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		1/3 (33.3%)		1/1 (100%)
Cardiac disorders
Myopericarditis	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Gastrointestinal disorders
Gastric hemorrhage	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Infections and infestations
Lung Infection	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Soft tissue infection	0/7 (0%)	0	0/3 (0%)	0	1/1 (100%)	1
Investigations
Alanine aminotransferase increased	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Aspartate aminotransferase increased	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Blood bilirubin increased	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	CPX-351 Treatment Induction Dose		CPX-351 Treatment Induction Dose + 1 Consolidation Dose		CPX-351 Treatment +2 Consolidation Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		3/3 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anemia	4/7 (57.1%)	19	2/3 (66.7%)	16	1/1 (100%)	6
Blood and lymphatic system disorders - Other, specify	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Febrile neutropenia	5/7 (71.4%)	6	2/3 (66.7%)	2	1/1 (100%)	2
Cardiac disorders
Cardiac disorders - Other	0/7 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
Chest pain - cardiac	0/7 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
Pericardial effusion	0/7 (0%)	0	2/3 (66.7%)	3	0/1 (0%)	0
Sinus tachycardia	1/7 (14.3%)	2	1/3 (33.3%)	1	0/1 (0%)	0
Cardiac troponin T increased	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Eye disorders
Blurred vision	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Eye disorders -Other	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Photophobia	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Gastrointestinal disorders
Abdominal Pain	4/7 (57.1%)	7	0/3 (0%)	0	0/1 (0%)	0
Constipation	2/7 (28.6%)	2	1/3 (33.3%)	1	0/1 (0%)	0
Diarrhea	3/7 (42.9%)	3	0/3 (0%)	0	0/1 (0%)	0
Dry mouth	1/7 (14.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Gingival pain	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Lower gastrointestinal hemorrhage	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Mucositis oral	2/7 (28.6%)	5	0/3 (0%)	0	0/1 (0%)	0
Nausea	2/7 (28.6%)	4	3/3 (100%)	7	0/1 (0%)	0
Oral hemorrhage	0/7 (0%)	0	2/3 (66.7%)	4	0/1 (0%)	0
Rectal pain	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Vomiting	3/7 (42.9%)	3	1/3 (33.3%)	1	0/1 (0%)	0
General disorders
Chills	3/7 (42.9%)	5	1/3 (33.3%)	1	0/1 (0%)	0
Edema limbs	1/7 (14.3%)	2	2/3 (66.7%)	3	1/1 (100%)	1
Fatigue	0/7 (0%)	0	1/3 (33.3%)	4	1/1 (100%)	1
Fever	1/7 (14.3%)	7	2/3 (66.7%)	2	0/1 (0%)	0
General disorders and administration site conditions - Other	1/7 (14.3%)	3	2/3 (66.7%)	6	0/1 (0%)	0
Infusion related reaction	1/7 (14.3%)	2	1/3 (33.3%)	2	0/1 (0%)	0
Localized edema	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Malaise	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Pain	1/7 (14.3%)	2	3/3 (100%)	8	0/1 (0%)	0
Hepatobiliary disorders
Hepatobiliary disorders - Other	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Immune system disorders
Immune system disorders - other	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Infections and infestations
Bronchial infection	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Infections and infestations - Other	2/7 (28.6%)	2	0/3 (0%)	0	0/1 (0%)	0
Lung infection	2/7 (28.6%)	3	0/3 (0%)	0	1/1 (100%)	1
Mucosal infection	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Sepsis	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Sinusitis	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Skin infection	2/7 (28.6%)	5	0/3 (0%)	0	0/1 (0%)	0
Soft tissue infection	0/7 (0%)	0	0/3 (0%)	0	1/1 (100%)	2
Papulopustular rash	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Injury, poisoning and procedural complications
Bruising	1/7 (14.3%)	1	1/3 (33.3%)	2	0/1 (0%)	0
Fall	1/7 (14.3%)	1	1/3 (33.3%)	3	0/1 (0%)	0
Investigations
Alanine aminotransferase increased	3/7 (42.9%)	6	0/3 (0%)	0	0/1 (0%)	0
Alkaline phosphatase increased	2/7 (28.6%)	3	1/3 (33.3%)	1	0/1 (0%)	0
Aspartate aminotransferase increased	1/7 (14.3%)	1	2/3 (66.7%)	7	0/1 (0%)	0
Blood bilirubin increased	1/7 (14.3%)	1	1/3 (33.3%)	2	0/1 (0%)	0
Creatinine increased	0/7 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0
Electrocardiogram QT corrected interval prolonged	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Investigations - Other	1/7 (14.3%)	1	1/3 (33.3%)	3	0/1 (0%)	0
Lipase increased	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Neutrophil count decreased	6/7 (85.7%)	17	3/3 (100%)	16	1/1 (100%)	7
Platelet count decreased	6/7 (85.7%)	24	3/3 (100%)	31	1/1 (100%)	12
Serum amylase increased	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Weight loss	1/7 (14.3%)	1	1/3 (33.3%)	2	0/1 (0%)	0
GGT Increased	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Metabolism and nutrition disorders
Anorexia	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Hypercalcemia	1/7 (14.3%)	2	1/3 (33.3%)	2	0/1 (0%)	0
Hyperglycemia	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Hyperkalemia	0/7 (0%)	0	2/3 (66.7%)	4	0/1 (0%)	0
Hypernatremia	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Hypoalbuminemia	1/7 (14.3%)	8	1/3 (33.3%)	3	0/1 (0%)	0
Hypokalemia	2/7 (28.6%)	2	0/3 (0%)	0	0/1 (0%)	0
Hypomagnesemia	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Hyponatremia	1/7 (14.3%)	1	2/3 (66.7%)	3	0/1 (0%)	0
Hypophosphatemia	2/7 (28.6%)	5	0/3 (0%)	0	0/1 (0%)	0
Metabolism and nutrition disorders - Other	1/7 (14.3%)	2	1/3 (33.3%)	1	1/1 (100%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)	4	0/3 (0%)	0	0/1 (0%)	0
Back pain	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Bone pain	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Buttock pain	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Generalized muscle weakness	2/7 (28.6%)	4	0/3 (0%)	0	0/1 (0%)	0
Myalgia	1/7 (14.3%)	1	1/3 (33.3%)	2	0/1 (0%)	0
Neck pain	1/7 (14.3%)	1	2/3 (66.7%)	3	1/1 (100%)	1
Musculoskeletal and connective tissue disorder - Other,	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Nervous system disorders
Dizziness	1/7 (14.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Headache	1/7 (14.3%)	8	3/3 (100%)	6	1/1 (100%)	1
Lethargy	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Peripheral sensory neuropathy	1/7 (14.3%)	1	1/3 (33.3%)	1	1/1 (100%)	1
Tremor	2/7 (28.6%)	2	0/3 (0%)	0	0/1 (0%)	0
Encephalopathy	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Facial muscle weakness	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Nervous system disorders - Other	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Psychiatric disorders
Anxiety	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Confusion	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Insomnia	1/7 (14.3%)	3	0/3 (0%)	0	0/1 (0%)	0
Hallucinations	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Renal and urinary disorders
Renal and urinary disorders -Other	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Atelectasis	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Bronchopulmonary hemorrhage	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Cough	1/7 (14.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Epistaxis	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Nasal congestion	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Pleural effusion	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Productive cough	0/7 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
Pulmonary edema	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Sleep apnea	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Respiratory failure	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Dyspnea	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/7 (14.3%)	1	0/3 (0%)	0	1/1 (100%)	1
Nail discoloration	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Periorbital edema	1/7 (14.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Pruritus	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Rash maculo-papular	4/7 (57.1%)	7	2/3 (66.7%)	2	0/1 (0%)	0
Skin and subcutaneous tissue disorders - Other	1/7 (14.3%)	1	1/3 (33.3%)	2	0/1 (0%)	0
Vascular disorders
Hematoma	2/7 (28.6%)	3	0/3 (0%)	0	1/1 (100%)	1
Hypertension	1/7 (14.3%)	5	1/3 (33.3%)	1	0/1 (0%)	0
Hypotension	1/7 (14.3%)	1	0/3 (0%)	0	0/1 (0%)	0
Thromboembolic event	1/7 (14.3%)	2	0/3 (0%)	0	0/1 (0%)	0
Superficial thrombophlebitis	0/7 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0

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.