Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for Relapsed or Refractory Acute Myeloid Leukemia

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03118466
• Collaborator: Celgene (Industry)
• Enrollment: 41
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 46.2
• Patients Per Site: 13.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This research study is evaluating how a drug called lenalidomide, given in combination with the standard chemotherapy regimen of Mitoxantrone, Etoposide, and Cytarabine, commonly referred to as MEC, works in individuals with either relapsed or refractory AML

Condition or Disease	Intervention/Treatment	Phase
AML	Drug: Etoposide; Drug: Cytarabine; Drug: Lenalidomide; Drug: Mitoxantrone	Phase 2

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved lenalidomide for this specific disease, but it has been approved for other uses, including for patients with multiple myeloma and some patients with myelodysplastic syndrome. This treatment is investigational because it is not approved by the FDA for patients with AML. Lenalidomide is a chemotherapy that also modulates the immune system, and is in a category of drugs called immunomodulatory drugs or IMIDs. Some research studies suggest that lenalidomide may be effective in patients with AML. Since the investigators know that many patients who receive MEC chemotherapy alone have less than desired response rates and overall shorter periods of remission (time free from leukemia) after treatment, the investigators are studying whether the addition of lenalidomide to MEC improves upon typical responses.

The combination of MEC (mitoxantrone, etoposide, and cytarabine) is a standard treatment option, commonly used for relapsed or refractory acute myeloid leukemia.

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Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for the Treatment of Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia
• Actual Study Start Date: Sep 25, 2017
• Actual Primary Completion Date: Aug 29, 2019
• Anticipated Study Completion Date: Aug 1, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lenalidomide and MEC chemotherapy Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study.

Drug: Etoposide; A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication.; Other Names: Toposar ; Drug: Cytarabine; Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA.; Other Names: Depocyt ; Drug: Lenalidomide; It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production; Other Names: REVLIMID ; Drug: Mitoxantrone; It interfere with cell reproduction; Other Names: Novantrone

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [up to 45 days]

   Proportion of patients who have achieve CR or CRp after treatment. Morphologic Complete Remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in Bone Marrow aspirate with marrow spicules, no persistent extramedullary disease, ANC >1000/mm3 and platelet count >100,000/mm3. Morphologic Complete Remission without platelet recovery (CRp): Defined as CR with the exception of platelet count < 100,000/mm3 (CRp).

Secondary Outcome Measures

1. Number of Patients That Achieved ANC Recovery [up to 45 days]

   The number of patients that achieved a neutrophil count of > 500/mm3 for 3 days within 45 of starting treatment

2. Number of Patients That Achieved Platelet Recovery [up to 45 days]

   The number of patients that achieved a stable platelet count > 20,000/mm3 for 3 days within 45 days of starting treatment

3. Treatment-related Mortality [50 days]

   Cumulative number of deaths not related to persistent or relapsed leukemia during treatment within 50 days of the start of treatment.

4. Transfusion Support: Number of Red Blood Cell and Platelet Transfusions [50 days]

   Number of red blood cell and platelet transfusions received within the first 50 days of treatment

5. Overall Survival [Up to 3 years]

   Overall survival is defined as time from diagnosis of disease until date of death or censored on the last known date alive if patients are still alive.

6. Relapse-Free Survival [Up to 3 years]

   Relapse-Free Survival is defined as time from diagnosis of disease until date of relapse, death, or censored on the last known date alive if patients are still alive.Relapse is defined by morphological evidence of the original malignancy consistent with pre-treatment features.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Acute myelogenous leukemia diagnosed by WHO criteria with one of the following (patients with biphenotypic leukemia are eligible, provided that the treating physician determines an AML treatment regimen is appropriate)

• Primary refractory disease following > 1cycle of chemotherapy, (such as hypomethylating agent or induction chemotherapy)

• First relapse or higher. Patients with primary or secondary acute myelogenous leukemia are eligible.

• Age 18-70 years old

• LVEF > 50 %

• ECOG Performance status 0-2

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

• Participants must have normal organ function as defined below, unless felt due to underlying disease and approved by the overall PI. Patients with Gilbert's disease may have total bilirubin up to < 3 x ULN.

• Creatinine < 2.0mg/dl

• Total bilirubin < 1.5 x ULN

• AST (SGOT) and ALT (SGPT) < 3 x ULN.

• Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until Day 5 of treatment.

• Patients must give voluntary written informed consent and HIPAA authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

• Patients may have had prior treatment for MDS or AML, including prior lenalidomide for MDS or AML or another condition.

• Patient may have had prior autologous or allogeneic transplant (family member, unrelated donor, or cord blood) if there is at least 90 days between transplant and study entry.

• Patients may also have had donor lymphocyte infusion if there is at least 60 days between donor lymphocyte infusion and study entry.

• Patients on immunosuppression are also eligible.

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to receiving treatment with lenalidomide, and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

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

• All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMs ® program. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program

Exclusion Criteria:

• Known hypersensitivity to thalidomide or lenalidomide (if applicable).

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

• Known seropositive for human immunodeficiency virus (HIV). HIV testing is not required. Hepatitis testing is not required.

• Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

• Any serious medical condition laboratory abnormality or psychiatric illness that would prevent the subject from signing the consent form.

• Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

• Patients with major surgery within 28 days prior to treatment.

• Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

• Patient has received an investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within 7 days of study entry.

• Patients with acute promyelocytic leukemia.

• Females who are pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02062
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Massachusetts general Hospital	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Massachusetts General Hospital
• Celgene

Investigators

• Principal Investigator: Andrew Brunner, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 27, 2019

More Information

Publications

None provided.

• Responsible Party: Andrew Mark Brunner, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03118466
• Other Study ID Numbers: 16-574
• First Posted: Apr 18, 2017
• Last Update Posted: Feb 3, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Andrew Mark Brunner, MD, Principal Investigator, Massachusetts General Hospital: AML
• Additional relevant MeSH terms: Leukemia, Myeloid, Acute; Cytarabine; Etoposide; Mitoxantrone; Lenalidomide

Study Results

Participant Flow

Pre-assignment Detail	One patient came off study prior to receiving any treatment and was replaced. A total of 40 patients received study treatment.

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	17 42.5%
Male	23 57.5%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	Proportion of patients who have achieve CR or CRp after treatment. Morphologic Complete Remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in Bone Marrow aspirate with marrow spicules, no persistent extramedullary disease, ANC >1000/mm3 and platelet count >100,000/mm3. Morphologic Complete Remission without platelet recovery (CRp): Defined as CR with the exception of platelet count < 100,000/mm3 (CRp).
Time Frame	up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Measure Participants	40
Count of Participants [Participants]	19 47.5%

2. Secondary Outcome

Title	Number of Patients That Achieved ANC Recovery
Description	The number of patients that achieved a neutrophil count of > 500/mm3 for 3 days within 45 of starting treatment
Time Frame	up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Measure Participants	40
Count of Participants [Participants]	25 62.5%

3. Secondary Outcome

Title	Number of Patients That Achieved Platelet Recovery
Description	The number of patients that achieved a stable platelet count > 20,000/mm3 for 3 days within 45 days of starting treatment
Time Frame	up to 45 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Measure Participants	40
Count of Participants [Participants]	27 67.5%

4. Secondary Outcome

Title	Treatment-related Mortality
Description	Cumulative number of deaths not related to persistent or relapsed leukemia during treatment within 50 days of the start of treatment.
Time Frame	50 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Measure Participants	40
Count of Participants [Participants]	2 5%

5. Secondary Outcome

Title	Transfusion Support: Number of Red Blood Cell and Platelet Transfusions
Description	Number of red blood cell and platelet transfusions received within the first 50 days of treatment
Time Frame	50 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Measure Participants	40
Platelet Transfusions	7
Red Blood Cell Transfusions	9

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from diagnosis of disease until date of death or censored on the last known date alive if patients are still alive.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
Measure Participants	40
Median (95% Confidence Interval) [Months]	16

7. Secondary Outcome

Title	Relapse-Free Survival
Description	Relapse-Free Survival is defined as time from diagnosis of disease until date of relapse, death, or censored on the last known date alive if patients are still alive.Relapse is defined by morphological evidence of the original malignancy consistent with pre-treatment features.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From the start of treatment until 30 days after the end of study treatment, up to 3 years
Arm/Group Title	Lenalidomide and MEC Chemotherapy
Arm/Group Description	Lenalidomide is taken orally on a daily basis days 1-10. Mitoxantrone, Etoposide, and Cytarabine are administered intravenously on a daily basis for days 4 through 8 of the treatment. There is only one cycle of treatment in this study. Etoposide: A Drug that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication. Cytarabine: Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Lenalidomide: It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing the status of the immune system, or decreasing cytokine and growth factor production Mitoxantrone: It interfere with cell reproduction
All Cause Mortality
	Lenalidomide and MEC Chemotherapy
	Affected / at Risk (%)	# Events
Total	15/40 (37.5%)
Serious Adverse Events
	Lenalidomide and MEC Chemotherapy
	Affected / at Risk (%)	# Events
Total	19/40 (47.5%)
Gastrointestinal disorders
Colonic obstruction	1/40 (2.5%)	1
Mucositis oral	1/40 (2.5%)	1
Small intestinal obstruction	1/40 (2.5%)	1
Hepatobiliary disorders
Hepatic failure	1/40 (2.5%)	5
Infections and infestations
Abdominal infection	1/40 (2.5%)	1
Hepatic infection	1/40 (2.5%)	1
Sepsis	1/40 (2.5%)	3
Infections and infestations - Other, candidemia sepsis	1/40 (2.5%)	1
Infections and infestations - Other, Enterococcus faecium bacteremia	1/40 (2.5%)	1
Investigations
Blood bilirubin increased	1/40 (2.5%)	2
Creatinine increased	1/40 (2.5%)	1
Ejection fraction decreased	1/40 (2.5%)	1
Nervous system disorders
Encephalopathy	1/40 (2.5%)	1
Intracranial hemorrhage	1/40 (2.5%)	1
Renal and urinary disorders
Acute kidney injury	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/40 (2.5%)	1
Hypoxia	1/40 (2.5%)	1
Pleural effusion	1/40 (2.5%)	1
Respiratory failure	1/40 (2.5%)	1
Vascular disorders
Hypotension	1/40 (2.5%)	3
Other (Not Including Serious) Adverse Events
	Lenalidomide and MEC Chemotherapy
	Affected / at Risk (%)	# Events
Total	40/40 (100%)
Blood and lymphatic system disorders
Anemia	20/40 (50%)	33
Febrile neutropenia	27/40 (67.5%)	37
Cardiac disorders
Sinus bradycardia	2/40 (5%)	2
Sinus tachycardia	5/40 (12.5%)	7
Eye disorders
Blurred vision	4/40 (10%)	4
Dry eye	3/40 (7.5%)	3
Gastrointestinal disorders
Abdominal distension	2/40 (5%)	2
Abdominal pain	11/40 (27.5%)	21
Bloating	2/40 (5%)	3
Colitis	5/40 (12.5%)	6
Constipation	10/40 (25%)	12
Diarrhea	22/40 (55%)	31
Dry mouth	4/40 (10%)	4
Dyspepsia	3/40 (7.5%)	3
Enterocolitis	2/40 (5%)	2
Esophageal pain	2/40 (5%)	2
Esophagitis	2/40 (5%)	2
Fecal incontinence	2/40 (5%)	2
Gastroesophageal reflux disease	4/40 (10%)	4
Gingival pain	2/40 (5%)	2
Hemorrhoids	7/40 (17.5%)	9
Lower gastrointestinal hemorrhage	2/40 (5%)	2
Mucositis oral	10/40 (25%)	12
Nausea	22/40 (55%)	27
Oral pain	4/40 (10%)	5
Rectal pain	5/40 (12.5%)	10
Typhlitis	2/40 (5%)	2
Vomiting	12/40 (30%)	14
General disorders
Chills	5/40 (12.5%)	5
Edema face	4/40 (10%)	5
Edema limbs	15/40 (37.5%)	17
Fatigue	20/40 (50%)	25
Fever	16/40 (40%)	21
Malaise	3/40 (7.5%)	3
Non-cardiac chest pain	2/40 (5%)	2
Infections and infestations
Catheter related infection	5/40 (12.5%)	5
Lung infection	6/40 (15%)	7
Skin infection	4/40 (10%)	4
Investigations
Alanine aminotransferase increased	11/40 (27.5%)	21
Alkaline phosphatase increased	5/40 (12.5%)	9
Aspartate aminotransferase increased	10/40 (25%)	16
Blood bilirubin increased	8/40 (20%)	17
Creatinine increased	3/40 (7.5%)	3
INR increased	3/40 (7.5%)	5
Lymphocyte count decreased	3/40 (7.5%)	6
Neutrophil count decreased	12/40 (30%)	21
Platelet count decreased	22/40 (55%)	63
Weight loss	3/40 (7.5%)	8
White blood cell decreased	5/40 (12.5%)	10
Metabolism and nutrition disorders
Anorexia	18/40 (45%)	29
Hypercalcemia	2/40 (5%)	2
Hypertriglyceridemia	2/40 (5%)	2
Hypoalbuminemia	9/40 (22.5%)	10
Hypocalcemia	9/40 (22.5%)	10
Hypokalemia	13/40 (32.5%)	38
Hypomagnesemia	6/40 (15%)	7
Hyponatremia	6/40 (15%)	7
Hypophosphatemia	14/40 (35%)	30
Musculoskeletal and connective tissue disorders
Back pain	6/40 (15%)	7
Bone pain	5/40 (12.5%)	5
Generalized muscle weakness	4/40 (10%)	4
Myalgia	2/40 (5%)	2
Neck pain	3/40 (7.5%)	3
Pain in extremity	4/40 (10%)	4
Musculoskeletal and connective tissue disorder -	2/40 (5%)	2
Nervous system disorders
Depressed level of consciousness	2/40 (5%)	2
Dizziness	9/40 (22.5%)	11
Dysgeusia	4/40 (10%)	5
Headache	10/40 (25%)	13
Paresthesia	2/40 (5%)	2
Somnolence	2/40 (5%)	2
Syncope	4/40 (10%)	4
Psychiatric disorders
Anxiety	6/40 (15%)	6
Depression	3/40 (7.5%)	3
Insomnia	11/40 (27.5%)	12
Renal and urinary disorders
Hematuria	3/40 (7.5%)	3
Reproductive system and breast disorders
Vaginal hemorrhage	2/40 (5%)	3
Respiratory, thoracic and mediastinal disorders
Cough	12/40 (30%)	16
Dyspnea	8/40 (20%)	8
Epistaxis	4/40 (10%)	4
Hiccups	3/40 (7.5%)	3
Hypoxia	4/40 (10%)	5
Nasal congestion	2/40 (5%)	3
Skin and subcutaneous tissue disorders
Pruritus	9/40 (22.5%)	10
Rash maculo-papular	13/40 (32.5%)	22
Vascular disorders
Flushing	3/40 (7.5%)	3
Hematoma	2/40 (5%)	2
Hypertension	2/40 (5%)	2
Hypotension	17/40 (42.5%)	22
Thromboembolic event	3/40 (7.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.