Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01496976
• Collaborator: Novartis (Industry), Celgene Corporation (Industry)
• Enrollment: 45
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 135
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The main purpose of this study is to see if ofatumumab with methylprednisolone followed by additional treatment with ofatumumab and lenalidomide can help people with Chronic Lymphocytic Leukemia (CLL) get rid of their CLL for a long period of time. Researchers also want to find out if the combination of ofatumumab with methylprednisolone followed by additional treatment with ofatumumab and lenalidomide is safe and tolerable.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma	Drug: High Dose Methylprednisolone (HDMP); Drug: Ofatumumab; Drug: Lenalidomide	Phase 2

Detailed Description

This is a phase II, single institution, and non-randomized study of patients with untreated CLL/SLL, utilizing a two-stage trial design. The primary endpoint for this trial is the combined complete and partial response rate (at 3 months-the end of cycle 3) to the protocol therapy. We anticipate this trial will have a complete response (CR) and partial response (PR) rate of at least 80%.

A two-stage design is employed for this trial. The null/unacceptable CR+PR response rate is ≤ 60% while the anticipated true response rate to the protocol treatment is at least 80% for each disease cohort. At the first stage, 26 patients will be accrued to the trial. If 15 or fewer of these patients respond, then the trial will be terminated early and the response rate to the protocol treatment will be deemed unacceptable (≤ 60%). Otherwise, if more than 15 patients respond during the first stage, an additional 19 patients will be enrolled to this trial during stage 2 for a total of 45 patients. If 32 or fewer of these 45 patients respond to the protocol treatment at the end of stage 2, no further investigation of the protocol treatment is considered warranted. On the other hand, if more than 32 patients out of the 45 enrolled patients respond, the protocol treatment will be considered promising. If the true response rate is ≤ 60%, the probability of ending the trial at stage 1 is 0.48. If, however, the true response rate is at least 80%, then the probability of ending the trial at stage 1 is only 0.01. This two-stage design has an overall alpha level of 0.045 and a power of 0.90.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Untreated CLL/SLL The HiLOG Trial
• Actual Study Start Date: Mar 30, 2012
• Actual Primary Completion Date: Oct 6, 2021
• Anticipated Study Completion Date: Jul 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Immunotherapy Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide

Drug: High Dose Methylprednisolone (HDMP); HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8.; Other Names: HDMP ; Drug: Ofatumumab; Ofatumumab infusion will be administered immediately after HDMP.; Other Names: Arzerra® ; Drug: Lenalidomide; The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.; Other Names: Revlimid® IMiD® compound

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Response (CR) [3 Months]

   Number of participants with complete response, the disappearance of all signs of cancer in response to treatment.

2. Number of Participants With Partial Response (PR) [3 Months]

   The primary endpoint for this trial is the combined complete and partial response rate to the protocol therapy at 3 months, which is also the end of Cycle 3. The objective response (CR+PR) rate will be summarized using both a point estimate and its exact confidence interval based on the binomial distribution.

Secondary Outcome Measures

1. Rate of Progression/Relapse Free Survival (PFS) [Up to 56 months]

   Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier.

2. Number of Participants With Overall Survival (OS) [36 Months]

   Overall survival will be summarized with the Kaplan-Meier curve.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form

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

• Patients must have histologically or cytologically confirmed CD5+/CD20+ B-Cell chronic lymphocytic leukemia or small lymphocytic lymphoma. The diagnosis of CLL is based upon the National Comprehensive Cancer Network (NCCN) guidelines. Any outside pathology slides used as inclusion criteria for the patient will be reviewed at this institution to confirm the diagnosis. The patient must meet all of the following CLL criteria to participate in this study: absolute lymphocyte count > 5000/μL; CD20+ and CD5+; Bone marrow lymphocytes ≥ 30%; Or previous confirmed diagnosis of CLL/SLL with less than 5000/μl or less than 30% lymphocytes in bone marrow.

• Patients are eligible if they have stage III or IV disease. Patients with stage 0, I or II disease will be eligible if they have evidence of active disease defined as one or more of the following signs/symptoms: Documented weight loss of ≥ 10% over a 6 month period; Febrile episodes of 38 degrees Celsius (100.5 degrees F) or greater for greater than 2 weeks without evidence of infection; Massive or progressive splenomegaly defined as > 6 cm below the left costal margin; Massive (> 10 cm in longest diameter) or progressive lymphadenopathy.

• Patient has not received any prior treatment for CLL in the past.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry

• Laboratory test results within these ranges: Absolute neutrophil count ≥ 1000/mm³; Platelet count ≥ 50,000 /mm³; Renal function assessed by calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula; Total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤ 2.5 x ULN; Alkaline phosphatase <2.5 x ULN

• Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

• All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of REMS®.

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) 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.

• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin).

Exclusion Criteria:

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

• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).

• Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Evidence of laboratory Tumor Lysis Syndrome (TLS) by Cairo-Bishop Definition. Patients may be enrolled upon correction of electrolyte abnormalities.

• Use of any other experimental drug or therapy within 28 days of baseline

• Known hypersensitivity to thalidomide

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

• Any prior use of lenalidomide

• Concurrent use of other anti-cancer agents or treatments

• Known seropositive for or active viral infection with human immunodeficiency virus (HIV)

• Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the patient will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the patient can be included. Patients who are seropositive because of hepatitis B virus vaccine are eligible. Consult with a physician experienced in care & management of subjects with hepatitis B to manage/treat subjects who are anti-HBc positive.

• Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result

• Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) are ineligible.

• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C

• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae

• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to randomization, congestive heart failure [New York Heart Association (NYHA) III-IV], and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities

• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient

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
• Novartis
• Celgene Corporation

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 2, 2017

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: NCT01496976
• Other Study ID Numbers: MCC-16622; COMB157BUS21T; RV-CLL-PI-0560
• First Posted: Dec 22, 2011
• Last Update Posted: Aug 17, 2022
• Last Verified: Aug 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: leukemia; lymphoma; consolidative therapy; combination regimen; CLL; SLL
• Additional relevant MeSH terms: Leukemia, Lymphocytic, Chronic, B-Cell; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Lenalidomide; Ofatumumab; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Period Title: Overall Study
STARTED	45
COMPLETED	44
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Overall Participants	45
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 55.6%
>=65 years	20 44.4%
Sex: Female, Male (Count of Participants)
Female	17 37.8%
Male	28 62.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	45 100%
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	0 0%
White	44 97.8%
More than one race	0 0%
Unknown or Not Reported	1 2.2%
Region of Enrollment (participants) [Number]
United States	45 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Response (CR)
Description	Number of participants with complete response, the disappearance of all signs of cancer in response to treatment.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

number of evaluable participants

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Measure Participants	44
Count of Participants [Participants]	1 2.2%

2. Primary Outcome

Title	Number of Participants With Partial Response (PR)
Description	The primary endpoint for this trial is the combined complete and partial response rate to the protocol therapy at 3 months, which is also the end of Cycle 3. The objective response (CR+PR) rate will be summarized using both a point estimate and its exact confidence interval based on the binomial distribution.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Measure Participants	44
Number [participants]	33 73.3%

3. Secondary Outcome

Title	Rate of Progression/Relapse Free Survival (PFS)
Description	Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier.
Time Frame	Up to 56 months

Outcome Measure Data

Analysis Population Description

evaluable participants

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Measure Participants	24
Median (95% Confidence Interval) [months]	54.4

4. Secondary Outcome

Title	Number of Participants With Overall Survival (OS)
Description	Overall survival will be summarized with the Kaplan-Meier curve.
Time Frame	36 Months

Outcome Measure Data

Analysis Population Description

evaluable participants

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Measure Participants	24
Number [participants]	24 53.3%

Adverse Events

Time Frame	Adverse events collected from day 1 up to 30 days after cycle 12, 3 years and 6 months
Arm/Group Title	Immunotherapy
Arm/Group Description	Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide High Dose Methylprednisolone (HDMP): HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8. Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. Lenalidomide: The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
All Cause Mortality
	Immunotherapy
	Affected / at Risk (%)	# Events
Total	6/45 (13.3%)
Serious Adverse Events
	Immunotherapy
	Affected / at Risk (%)	# Events
Total	11/45 (24.4%)
Blood and lymphatic system disorders
Febrile Neutropenia	4/45 (8.9%)	4
Cardiac disorders
Cardiac arrest	1/45 (2.2%)	1
Gastrointestinal disorders
Small intestinal obstruction	1/45 (2.2%)	1
Diverticulitis	1/45 (2.2%)	1
General disorders
Fever	2/45 (4.4%)	4
Non-cardiac chest pain	1/45 (2.2%)	1
Pain	1/45 (2.2%)	2
Immune system disorders
Allergic Reaction	1/45 (2.2%)	1
Infections and infestations
Infections and infestations - Other	1/45 (2.2%)	1
Lung infection	1/45 (2.2%)	1
Metabolism and nutrition disorders
Hypercalcemia	2/45 (4.4%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	1/45 (2.2%)	1
Renal and urinary disorders
Acute kidney injury	2/45 (4.4%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/45 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Immunotherapy
	Affected / at Risk (%)	# Events
Total	45/45 (100%)
Blood and lymphatic system disorders
Anemia	12/45 (26.7%)	20
Blood and lymphatic system disorders - Other	7/45 (15.6%)	9
Leukocytosis	5/45 (11.1%)	6
Febrile neutropenia	4/45 (8.9%)	4
Lymph node pain	3/45 (6.7%)	5
Thrombotic thrombocytopenic purpura	1/45 (2.2%)	1
Cardiac disorders
Cardiac disorders - Other	8/45 (17.8%)	11
Sinus bradycardia	3/45 (6.7%)	6
Sinus tachycardia	3/45 (6.7%)	4
Cardiac arrest	1/45 (2.2%)	1
Chest pain - cardiac	1/45 (2.2%)	1
Ear and labyrinth disorders
Tinnitus	2/45 (4.4%)	2
Ear and labyrinth disorders - Other	1/45 (2.2%)	1
Ear pain	1/45 (2.2%)	2
Vertigo	1/45 (2.2%)	1
Eye disorders
Eye disorders - Other	15/45 (33.3%)	18
Blurred vision	7/45 (15.6%)	7
Dry eye	5/45 (11.1%)	6
Watering eyes	2/45 (4.4%)	2
Cataract	1/45 (2.2%)	2
Floaters	1/45 (2.2%)	1
Vitreous hemorrhage	1/45 (2.2%)	1
Gastrointestinal disorders
Diarrhea	24/45 (53.3%)	48
Constipation	20/45 (44.4%)	33
Nausea	20/45 (44.4%)	33
Dyspepsia	10/45 (22.2%)	15
Abdominal Pain	9/45 (20%)	10
Gastrointestinal disorders - Other	9/45 (20%)	9
Vomiting	9/45 (20%)	12
Dry mouth	6/45 (13.3%)	10
Dysphagia	5/45 (11.1%)	5
Flatulence	4/45 (8.9%)	5
Gastroesophageal reflux disease	4/45 (8.9%)	4
Oral pain	4/45 (8.9%)	4
Bloating	3/45 (6.7%)	4
Stomach pain	3/45 (6.7%)	3
Gastrointestinal pain	2/45 (4.4%)	2
Rectal hemorrhage	2/45 (4.4%)	2
Abdominal distension	1/45 (2.2%)	1
Anal pain	1/45 (2.2%)	1
Gastritis	1/45 (2.2%)	4
Hemorrhoids	1/45 (2.2%)	2
Mucositis oral	1/45 (2.2%)	1
Oral hemorrhage	1/45 (2.2%)	2
Small intestinal obstruction	1/45 (2.2%)	1
General disorders
Fatigue	22/45 (48.9%)	40
Pain	18/45 (40%)	30
Infusion related reaction	16/45 (35.6%)	20
Edema limbs	14/45 (31.1%)	24
Fever	13/45 (28.9%)	17
Chills	12/45 (26.7%)	15
Flu like symptoms	11/45 (24.4%)	14
General disorders & administration site conditions-Other	7/45 (15.6%)	8
Irritability	4/45 (8.9%)	4
Non-cardiac chest pain	3/45 (6.7%)	4
Edema face	2/45 (4.4%)	2
Edema trunk	2/45 (4.4%)	7
Gait disturbance	2/45 (4.4%)	2
Injection site reaction	2/45 (4.4%)	2
Malaise	2/45 (4.4%)	2
Localized edema	1/45 (2.2%)	1
Immune system disorders
Allergic reaction	4/45 (8.9%)	7
Infections and infestations
Upper respiratory infection	17/45 (37.8%)	23
Sinusitis	14/45 (31.1%)	16
Infections and infestations - Other	9/45 (20%)	9
Urinary tract infection	5/45 (11.1%)	6
Rash pustular	2/45 (4.4%)	2
Skin infection	2/45 (4.4%)	2
Bronchial infection	1/45 (2.2%)	1
Conjunctivitis infective	1/45 (2.2%)	1
Eye infection	1/45 (2.2%)	1
Lung infection	1/45 (2.2%)	2
Mucosal infection	1/45 (2.2%)	1
Otitis media	1/45 (2.2%)	1
Papulopustular rash	1/45 (2.2%)	1
Rhinitis infective	1/45 (2.2%)	1
Tooth infection	1/45 (2.2%)	1
Injury, poisoning and procedural complications
Bruising	6/45 (13.3%)	7
Injury, poisoning and procedural complications - Other	3/45 (6.7%)	6
Fall	1/45 (2.2%)	1
Investigations
Neutrophil count decreased	37/45 (82.2%)	274
White blood cell decreased	29/45 (64.4%)	130
Platelet count decreased	16/45 (35.6%)	46
Investigations -Other	11/45 (24.4%)	22
Alanine aminotransferase increased	10/45 (22.2%)	24
Aspartate aminotransferase increased	8/45 (17.8%)	13
Lymphocycte count decreased	6/45 (13.3%)	7
Creatinine increased	5/45 (11.1%)	6
Weight loss	4/45 (8.9%)	6
Alkaline phosphatase increased	2/45 (4.4%)	2
Blood bilirubin increased	2/45 (4.4%)	3
Weight gain	2/45 (4.4%)	2
Lymphocyte count increased	1/45 (2.2%)	1
Urine output decreased	1/45 (2.2%)	1
Metabolism and nutrition disorders
Metabolism and nutrition disorders -Other	34/45 (75.6%)	108
Hyperkalemia	16/45 (35.6%)	29
Hyperglycemia	15/45 (33.3%)	21
Anorexia	12/45 (26.7%)	15
Hypermagnesemia	7/45 (15.6%)	8
Hyperuricemia	6/45 (13.3%)	7
Hypocalcemia	6/45 (13.3%)	18
Hypoglycemia	5/45 (11.1%)	9
Hypercalcemia	4/45 (8.9%)	11
Hypoalbuminemia	4/45 (8.9%)	4
Hypokalemia	4/45 (8.9%)	11
Dehydration	3/45 (6.7%)	4
Hypophosphatemia	3/45 (6.7%)	4
Hyponatremia	2/45 (4.4%)	2
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	14/45 (31.1%)	17
Pain in extremity	13/45 (28.9%)	14
Back pain	12/45 (26.7%)	20
Myalgia	11/45 (24.4%)	13
Musculoskeletal and connective tissue disorder - Other	8/45 (17.8%)	13
Arthralgia	7/45 (15.6%)	10
Bone pain	4/45 (8.9%)	5
Muscle weakness upper limb	3/45 (6.7%)	3
Flank pain	2/45 (4.4%)	3
Muscle weakness lower limb	2/45 (4.4%)	2
Arthritis	1/45 (2.2%)	1
Chest wall pain	1/45 (2.2%)	1
Joint effusion	1/45 (2.2%)	1
Muscle weakness right-sided	1/45 (2.2%)	1
Neck pain	1/45 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	14/45 (31.1%)	19
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	2/45 (4.4%)	2
Nervous system disorders
Peripheral sensory neuropathy	22/45 (48.9%)	34
Headache	19/45 (42.2%)	32
Movements involuntary	17/45 (37.8%)	26
Dizziness	15/45 (33.3%)	23
Paresthesia	13/45 (28.9%)	27
Dysgeusia	9/45 (20%)	14
Concentration impairment	7/45 (15.6%)	7
Memory impairment	7/45 (15.6%)	8
Nervous system disorders - Other	6/45 (13.3%)	7
Tremor	6/45 (13.3%)	8
Akathisia	1/45 (2.2%)	1
Ataxia	1/45 (2.2%)	1
Dysarthria	1/45 (2.2%)	1
Dyphasia	1/45 (2.2%)	1
Lethargy	1/45 (2.2%)	5
Sinus pain	1/45 (2.2%)	1
Psychiatric disorders
Insomnia	31/45 (68.9%)	53
Anxiety	9/45 (20%)	14
Depression	7/45 (15.6%)	8
Psychiatric disorders - Other	7/45 (15.6%)	9
Agitation	4/45 (8.9%)	5
Confusion	2/45 (4.4%)	3
Euphoria	1/45 (2.2%)	1
Libido decreased	1/45 (2.2%)	1
Mania	1/45 (2.2%)	4
Renal and urinary disorders
Renal and urinary disorders - Other	7/45 (15.6%)	11
Urinary frequency	5/45 (11.1%)	5
Urinary retention	2/45 (4.4%)	2
Acute kidney injury	1/45 (2.2%)	3
Bladder spasm	1/45 (2.2%)	1
Chronic kidney disease	1/45 (2.2%)	1
Hematuria	1/45 (2.2%)	1
Renal calculi	1/45 (2.2%)	2
Urinary incontinence	1/45 (2.2%)	3
Urinary tract pain	1/45 (2.2%)	1
Urine discoloration	1/45 (2.2%)	1
Reproductive system and breast disorders
Reproductive system and breast disorders - Other	2/45 (4.4%)	2
Pelvic pain	1/45 (2.2%)	1
Perineal pain	1/45 (2.2%)	1
Vaginal hemorrhage	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Cough	18/45 (40%)	23
Dyspnea	12/45 (26.7%)	19
Sore throat	12/45 (26.7%)	13
Nasal congestion	11/45 (24.4%)	12
Productive cough	8/45 (17.8%)	9
Allergic rhinitis	7/45 (15.6%)	8
Hoarseness	6/45 (13.3%)	7
Respiratory, thoracic and mediastinal disorders - Other	5/45 (11.1%)	5
Hiccups	3/45 (6.7%)	3
Postnasal drip	3/45 (6.7%)	3
Epistaxis	2/45 (4.4%)	2
Pleural effusion	2/45 (4.4%)	2
Sinus disorder	2/45 (4.4%)	2
Bronchospasm	1/45 (2.2%)	1
Hypoxia	1/45 (2.2%)	1
Pneumonitis	1/45 (2.2%)	1
Voice alteration	1/45 (2.2%)	1
Wheezing	1/45 (2.2%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	19/45 (42.2%)	30
Skin and subcutaneous tissue disorders - Other	16/45 (35.6%)	25
Hyperhidrosis	15/45 (33.3%)	20
Pruritus	15/45 (33.3%)	25
Dry skin	14/45 (31.1%)	18
Erythema multiforme	6/45 (13.3%)	8
Alopecia	4/45 (8.9%)	4
Rash acneiform	4/45 (8.9%)	5
Skin hyperpigmentation	2/45 (4.4%)	2
Photosensitivity	1/45 (2.2%)	1
Skin ulceration	1/45 (2.2%)	1
Surgical and medical procedures
Surgical and medical procedures - Other	15/45 (33.3%)	26
Vascular disorders
Hypertension	19/45 (42.2%)	26
Flushing	6/45 (13.3%)	9
Hot flashes	5/45 (11.1%)	5
Hypotension	5/45 (11.1%)	8
Thromboembolic event	2/45 (4.4%)	2
Lymphedema	1/45 (2.2%)	1
Peripheral ischemia	1/45 (2.2%)	1
Vascular disorders - Other	1/45 (2.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.