Trial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom's Macroglobulinemia

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02400437
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 55
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This research study is evaluating a drug called ixazomib (also known as MLN9708) in combination with dexamethasone and rituximab (the regimen is called IDR) as a possible treatment for Waldenstrom's Macroglobulinemia (WM).

Condition or Disease	Intervention/Treatment	Phase
Waldenstrom's Macroglobulinemia	Drug: Ixazomib; Drug: Dexamethasone; Drug: Rituximab	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 regimen, IDR, to learn whether IDR works in treating a specific cancer. "Investigational" means that IDR is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if IDR is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved IDR for use in participants with your type of cancer.

Ixazomib is a drug that may kill or stop cancer cells from growing by blocking the proteasome within the cell, which is responsible for degrading or breaking down a variety of proteins. This type of drug is called a proteasome inhibitor.

Rituximab is a type of protein called an antibody that attacks the cluster of differentiation 20 (CD20), a protein found on B-cells like WM. Rituximab is approved by the FDA for treating non-Hodgkin lymphoma (NHL). Dexamethasone is a steroid and is similar to the hormones naturally produced by the adrenal glands; it prevents the release of substances that cause inflammation. Rituximab and dexamethasone are often used to treat WM, alone or in combination with other drugs. Combinations with rituximab, dexamethasone and other proteasome inhibitors have shown good response rates in WM participants. Ixazomib is a proteasome inhibitor; thus the investigator swill investigate if the combination of Ixazomib, Rituximab, and Dexamethasone is also active in WM.

In this research study, the investigators are combining a new treatment ixazomib with a standard regimen, rituximab and dexamethasone, to determine whether this combination (IDR) is effective and safe for participants with previously untreated WM.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom's Macroglobulinemia
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Nov 1, 2019
• Actual Study Completion Date: Nov 1, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IDR - IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase

Drug: Ixazomib; Doses given on Days 1, 8, and 15 in induction and maintenance cycles.; Other Names: MLN9708 ; Drug: Dexamethasone; Doses given on Days 1, 8, and 15 in induction and maintenance cycles.; Other Names: Decadron Dexasone, Diodex Hexadrol Maxidex ; Drug: Rituximab; Doses given on Day 1 of induction and maintenance cycles.; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Very Good Partial Response Rate (VGPR) for IDR [76 weeks]

   Rate of very good partial response or better in patients treated with IDR. VGPR is defined as a >90% reduction in serum IgM levels from baseline.

Secondary Outcome Measures

1. Overall Response Rate [2 Years]

   Overall response includes the rate of complete response (CR), partial response (PR), minimal response (MR), stabl disease (SD) and progressive disease (PD). Minor response is >25%-50% reduction in serum IgM from baseline. Partial Response is (>50-90% reduction in serum IgM from baseline. Very Good Partial Response is >90% reduction in serum IgM from baseline. Complete Response is resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly.

2. Progression-free Survival (PFS) [From start of treatment to time of disease progression, assessed up to 4 years after treatment start]

   Duration of time from start of treatment to disease progression. Progressive disease is defined as occurring when a >25% increase in serum IgM and an absolute 500mg/dL increase in IgM level occurs from the lowest attained response value, or progression of clinically significant disease related symptoms.

3. Overall Response Rate by MYD88 L265P and CXCR4-WHIM Status [2 Years]

   To evaluate the overall response rate of participants by MYD88 L265P and CXCR4-WHIM mutations in WM. Overall response is defined as achieving at least a minor response, or >25% reduction in serum IgM from baseline.

4. Time to Progression (TTP) [From start of treatment to time of disease progression, assessed up to 4 years after treatment start]

   Duration of time from start of treatment to time of disease progression.

5. Duration of Response (DOR) [From the time each participant achieved a response to time of disease progression, assessed up to 4 years after treatment start]

   The duration of response is measured from the time a participant achieved a response until the date of progression.

6. Time to Next Therapy (TTNT) [From start of treatment until the participant begins a new therapy, assessed up to 4 years after treatment start]

   Duration from start of protocol treatment to time of initiation of new therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female patients 18 years or older.

• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care.

• Female patients who:

• Are postmenopausal for at least 1 year before the screening visit, OR

• Are surgically sterile, OR

• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND

• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

• Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR

• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

• Clinicopathological diagnosis of WM (Owen 2003), with symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM (Kyle 2003), and measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of >2 times the upper limit of normal.

• Eastern Cooperative Oncology Group performance status of 0, 1, or 2.

• Patients must meet the following clinical laboratory criteria

• Absolute neutrophil count ≥1,000/mm3 and platelet count ≥75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.

• Total bilirubin ≤1.5 x the upper limit of the normal range (ULN).

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN.

• Calculated creatinine clearance ≥30 mL/min.

Exclusion Criteria:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.

• Major surgery within 14 days before enrollment.

• Central nervous system involvement.

• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.

• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.

• Systemic treatment, within 14 days before the first dose, with strong inhibitors of cytochrome P (CYP) 1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort.

• Known hepatitis B or C virus, or HIV infection.

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

• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.

• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Jorge J. Castillo, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 13, 2017

More Information

Publications

None provided.

• Responsible Party: Jorge J. Castillo, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT02400437
• Other Study ID Numbers: 14-559
• First Posted: Mar 27, 2015
• Last Update Posted: Sep 2, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Jorge J. Castillo, MD, Principal Investigator, Dana-Farber Cancer Institute: Waldenstrom's Macroglobulinemia
• Additional relevant MeSH terms: Waldenstrom Macroglobulinemia; Dexamethasone; Rituximab; Ixazomib

Study Results

Participant Flow

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Period Title: Overall Study
STARTED	26
COMPLETED	26
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Overall Participants	26
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 42.3%
>=65 years	15 57.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.5
Sex: Female, Male (Count of Participants)
Female	5 19.2%
Male	21 80.8%
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	26 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%
Mutational Status (Count of Participants)
MYD88 Mutated, CXCR4 Wild-type	11 42.3%
MYD88 Mutated, CXCR4 Mutated	15 57.7%

Outcome Measures

1. Primary Outcome

Title	Very Good Partial Response Rate (VGPR) for IDR
Description	Rate of very good partial response or better in patients treated with IDR. VGPR is defined as a >90% reduction in serum IgM levels from baseline.
Time Frame	76 weeks

Outcome Measure Data

Analysis Population Description

All participants who have received at least 1 cycle of therapy.

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Measure Participants	26
Count of Participants [Participants]	5 19.2%

2. Secondary Outcome

Title	Overall Response Rate
Description	Overall response includes the rate of complete response (CR), partial response (PR), minimal response (MR), stabl disease (SD) and progressive disease (PD). Minor response is >25%-50% reduction in serum IgM from baseline. Partial Response is (>50-90% reduction in serum IgM from baseline. Very Good Partial Response is >90% reduction in serum IgM from baseline. Complete Response is resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly.
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 cycle of therapy.

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Measure Participants	26
Count of Participants [Participants]	25 96.2%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Duration of time from start of treatment to disease progression. Progressive disease is defined as occurring when a >25% increase in serum IgM and an absolute 500mg/dL increase in IgM level occurs from the lowest attained response value, or progression of clinically significant disease related symptoms.
Time Frame	From start of treatment to time of disease progression, assessed up to 4 years after treatment start

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 cycle of therapy. Participants were followed for up to 2 years after treatment discontinuation.

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Measure Participants	26
Median (Full Range) [months]	33

4. Secondary Outcome

Title	Overall Response Rate by MYD88 L265P and CXCR4-WHIM Status
Description	To evaluate the overall response rate of participants by MYD88 L265P and CXCR4-WHIM mutations in WM. Overall response is defined as achieving at least a minor response, or >25% reduction in serum IgM from baseline.
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

Number of participants who achieved a response by mutational status

Arm/Group Title	MYD88 Mutated, CXCR4 Wild-type	MYD88 Mutated, CXCR4 Mutated
Arm/Group Description	Participants who were MYD88 mutated and did not have the CXCR4 mutation	Participants with both the MYD88 mutation and a CXCR4 mutation
Measure Participants	11	15
Count of Participants [Participants]	11 42.3%	14 NaN

5. Secondary Outcome

Title	Time to Progression (TTP)
Description	Duration of time from start of treatment to time of disease progression.
Time Frame	From start of treatment to time of disease progression, assessed up to 4 years after treatment start

Outcome Measure Data

Analysis Population Description

All participants who received 1 cycle of treatment.

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Measure Participants	26
Median (Full Range) [months]	33

6. Secondary Outcome

Title	Duration of Response (DOR)
Description	The duration of response is measured from the time a participant achieved a response until the date of progression.
Time Frame	From the time each participant achieved a response to time of disease progression, assessed up to 4 years after treatment start

Outcome Measure Data

Analysis Population Description

All participants who achieved a response to therapy.

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Measure Participants	25
Median (Full Range) [months]	33

7. Secondary Outcome

Title	Time to Next Therapy (TTNT)
Description	Duration from start of protocol treatment to time of initiation of new therapy.
Time Frame	From start of treatment until the participant begins a new therapy, assessed up to 4 years after treatment start

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
Measure Participants	26
Median (Full Range) [months]	39

Adverse Events

Time Frame	Adverse events were collected starting after the first dose of study medication through 30 days of last treatment, an average of 1.5 years.
Arm/Group Title	Ixazomib, Dexamethasone, Rituximab
Arm/Group Description	- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase Ixazomib: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Dexamethasone: Doses given on Days 1, 8, and 15 in induction and maintenance cycles. Rituximab: Doses given on Day 1 of induction and maintenance cycles.
All Cause Mortality
	Ixazomib, Dexamethasone, Rituximab
	Affected / at Risk (%)	# Events
Total	0/26 (0%)
Serious Adverse Events
	Ixazomib, Dexamethasone, Rituximab
	Affected / at Risk (%)	# Events
Total	4/26 (15.4%)
Cardiac disorders
Heart Failure	1/26 (3.8%)	1
General disorders
Failure to thrive	1/26 (3.8%)	1
Flu-like symptoms	1/26 (3.8%)	1
Infections and infestations
Sepsis	1/26 (3.8%)	1
Pneumonia	2/26 (7.7%)	2
Staph Aureus Bacteremia	1/26 (3.8%)	1
Metabolism and nutrition disorders
Dehydration	1/26 (3.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cell Carcinoma	1/26 (3.8%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	1/26 (3.8%)	1
Pleural Effusion	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	Ixazomib, Dexamethasone, Rituximab
	Affected / at Risk (%)	# Events
Total	25/26 (96.2%)
Blood and lymphatic system disorders
Anemia	1/26 (3.8%)	1
Cardiac disorders
Palpitations	1/26 (3.8%)	1
Sinus tachycardia	2/26 (7.7%)	2
Ventricular arrhythmia	1/26 (3.8%)	1
Ear and labyrinth disorders
Ear pain	1/26 (3.8%)	1
Hearing loss	1/26 (3.8%)	1
Tinnitus	2/26 (7.7%)	2
Eye disorders
Blurry vision	3/26 (11.5%)	3
Cataract	1/26 (3.8%)	1
Conjunctivitis	1/26 (3.8%)	1
Keratitis	1/26 (3.8%)	1
Retinal detachment	1/26 (3.8%)	1
Gastrointestinal disorders
Abdominal pain	1/26 (3.8%)	1
Bloating	2/26 (7.7%)	2
Constipation	4/26 (15.4%)	4
Diarrhea	6/26 (23.1%)	6
Dry mouth	1/26 (3.8%)	1
Dyspepsia	1/26 (3.8%)	1
Gastroesophageal reflux disease	2/26 (7.7%)	2
Gastroenteritis	1/26 (3.8%)	1
Nausea	9/26 (34.6%)	9
Rectal hemorrhage	2/26 (7.7%)	2
Vomiting	4/26 (15.4%)	4
General disorders
Chills	4/26 (15.4%)	4
Edema face	3/26 (11.5%)	3
Fatigue	9/26 (34.6%)	9
Fever	6/26 (23.1%)	6
Flu-like symptoms	1/26 (3.8%)	1
Feeling cold	1/26 (3.8%)	1
Sweats	1/26 (3.8%)	1
Infusion related reaction	9/26 (34.6%)	9
Malaise	1/26 (3.8%)	1
Non-cardiac chest pain	2/26 (7.7%)	2
Pain	2/26 (7.7%)	2
Infections and infestations
Pneumonia	1/26 (3.8%)	1
Skin infection	1/26 (3.8%)	1
Otitis externa	1/26 (3.8%)	1
Papulopustular rash	2/26 (7.7%)	2
Unspecified rash	1/26 (3.8%)	1
Sinusitis	1/26 (3.8%)	1
Upper respiratory infection	9/26 (34.6%)	9
Urinary tract infection	1/26 (3.8%)	1
Injury, poisoning and procedural complications
Fall	1/26 (3.8%)	1
Fracture	1/26 (3.8%)	1
Investigations
Neutrophil count decreased	1/26 (3.8%)	1
Weight gain	1/26 (3.8%)	1
Weight loss	1/26 (3.8%)	1
Metabolism and nutrition disorders
Anorexia	1/26 (3.8%)	1
Hyperglycemia	6/26 (23.1%)	6
Iron deficiency	1/26 (3.8%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/26 (3.8%)	1
Back pain	3/26 (11.5%)	3
Generalized muscle weakness	3/26 (11.5%)	3
Muscle weakness lower limb	1/26 (3.8%)	1
Muscle cramps	2/26 (7.7%)	2
Shoulder discomfort	1/26 (3.8%)	1
Myalgia	1/26 (3.8%)	1
Foot pain	1/26 (3.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid nodules	1/26 (3.8%)	1
Nervous system disorders
Dizziness	6/26 (23.1%)	6
Dysgeusia	3/26 (11.5%)	3
Headache	3/26 (11.5%)	3
Peripheral sensory neuropathy	7/26 (26.9%)	7
Presyncope	1/26 (3.8%)	1
Sinus pressure	1/26 (3.8%)	1
Psychiatric disorders
Anxiety	1/26 (3.8%)	1
Insomnia	8/26 (30.8%)	8
Restless legs	2/26 (7.7%)	2
Renal and urinary disorders
Urinary incontinence	1/26 (3.8%)	1
Reproductive system and breast disorders
Amenorrhea	1/26 (3.8%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/26 (7.7%)	2
Dyspnea	1/26 (3.8%)	1
Epistaxis	1/26 (3.8%)	1
Hiccups	1/26 (3.8%)	1
Nasal congestion	1/26 (3.8%)	1
Pleural effusion	1/26 (3.8%)	1
Sore throat	3/26 (11.5%)	3
Skin and subcutaneous tissue disorders
Hyperhidrosis	2/26 (7.7%)	2
Pruritis	1/26 (3.8%)	1
Rash maculopapular	5/26 (19.2%)	5
Skin ulceration	1/26 (3.8%)	1
Vascular disorders
Flushing	2/26 (7.7%)	2
Hematoma	2/26 (7.7%)	2
Hot flashes	1/26 (3.8%)	1
Hypotension	1/26 (3.8%)	1

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.