UARK 2014-14: Phase II Prospective Evaluation of Bone Remodeling During Ixazomib Treatment

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT02499081
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 32.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of Ixazomib on inducing osteoblast activation as measured by bone markers and imaging in patients with relapsed/refractory myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Ixazomib	Phase 2

Detailed Description

This is a phase II study designed to examine the bone anabolic effect of the next generation proteasome inhibitor, ixazomib, in relapsed/refractory myeloma patients. Treatment consists of Ixazomib 4 mg on days 1, 8, 15, 22 of a 28 day cycle, for a maximum of 6 cycles. Determination of relapsed/refractory disease as an entry criterion may be based on patient data obtained during or following the patient's most recent prior antineoplastic therapy. Treatment periods will be defined as 28-day cycles. Patients will be seen at regular intervals while they are participating in the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Prospective Evaluation of Bone Remodeling During Ixazomib Treatment Relapsed/Refractory Multiple Myeloma Patients
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: May 17, 2018
• Actual Study Completion Date: May 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixazomib Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles.	Drug: Ixazomib; Other Names: (MLN 9708)

Outcome Measures

Primary Outcome Measures

1. Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma. [Baseline, Treatment (28-day cycles for 6 cycles)]

   To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• 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 consent may be withdrawn by the patient 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.)

• Patients must have a diagnosis of relapsed/refractory multiple myeloma and must have received at least one line of prior therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.

• Patients must meet the following clinical laboratory criteria:

Absolute neutrophil count (ANC)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 bilirubin1.5 the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 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.

• Failure to have fully recovered (ie, Grade 1 toxicity) from the reversible effects of prior chemotherapy.

• Major surgery within 14 days before enrollment.

• Radiotherapy within 14 days before enrollment. If the involved field is small (in the opinion of the enrolling investigator), 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.

• Patients who have non-myeloma related bone disease that will interfere with the interpretation of the bone-related blood and radiology assessments, including Paget's disease, Rickets, Osteomalacia, and any other metastatic bone cancer.

• History of myeloma-related 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 of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.

• Ongoing or active systemic infection, known active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.

• 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 GI disease or history of 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.

• Patient has Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.

• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial.

• Patients who have taken bisphosphonate or RANK Ligand Inhibitor within 3 weeks from screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Science	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Maurizio Zangari, MD, University of Arkansas

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 15, 2017

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT02499081
• Other Study ID Numbers: 203444
• First Posted: Jul 15, 2015
• Last Update Posted: Jun 11, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Arkansas: Relapsed; Refractory; Proteasome Inhibitor
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Ixazomib

Study Results

Participant Flow

Arm/Group Title	Ixazomib
Arm/Group Description	Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles.
Period Title: Overall Study
STARTED	20
COMPLETED	1
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Ixazomib
Arm/Group Description	Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.91 (10.27)
Sex/Gender, Customized (participants) [Number]
Male	11 55%
Female	9 45%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 10%
Not Hispanic or Latino	18 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 10%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 20%
White	14 70%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma.
Description	To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma.
Time Frame	Baseline, Treatment (28-day cycles for 6 cycles)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ixazomib
Arm/Group Description	Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
Measure Participants	20
Median (95% Confidence Interval) [ng/ML]	20.00

Adverse Events

Time Frame	Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity).
Adverse Event Reporting Description	A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Arm/Group Title	Ixazomib
Arm/Group Description	Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
All Cause Mortality
	Ixazomib
	Affected / at Risk (%)	# Events
Total	15/20 (75%)
Serious Adverse Events
	Ixazomib
	Affected / at Risk (%)	# Events
Total	8/20 (40%)
Blood and lymphatic system disorders
Anemia	8/20 (40%)	32
Febrile Neutropenia	2/20 (10%)	3
Lymphocyte Count Decreased	8/20 (40%)	44
Neutrophil count decreased	2/20 (10%)	5
Platelet count decreased	6/20 (30%)	65
Wbc decrease (leukopenia)	2/20 (10%)	16
Gastrointestinal disorders
Vomiting	1/20 (5%)	1
Pain	1/20 (5%)	1
Metabolism and nutrition disorders
Hypermagnesemia	2/20 (10%)	5
Hypokalemia	2/20 (10%)	5
Hyponatremia	2/20 (10%)	5
Nervous system disorders
Headache	1/20 (5%)	1
Syncope	1/20 (5%)	1
Psychiatric disorders
Anxiety	1/20 (5%)	1
Vascular disorders
Hypertension	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Ixazomib
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Anemia	11/20 (55%)	158
Lymphocyte count decreased	5/20 (25%)	64
Neutrophil count decreased	4/20 (20%)	11
Platelet count decreased	14/20 (70%)	115
Wbc decrease (leukopenia)	10/20 (50%)	45
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	1/20 (5%)	1
Tinnitus	1/20 (5%)	1
Eye disorders
Blurred vision	1/20 (5%)	1
Dry eye	1/20 (5%)	1
Eye disorders - other	2/20 (10%)	2
Photophobia	1/20 (5%)	1
Watering eyes	2/20 (10%)	2
Gastrointestinal disorders
Constipation	2/20 (10%)	4
Diarrhea	9/20 (45%)	12
Dyspepsia	1/20 (5%)	1
Gastroesophageal reflux disease	1/20 (5%)	1
Gastrointestinal disorders - Other, specify	2/20 (10%)	2
Nausea	9/20 (45%)	9
Vomiting	3/20 (15%)	5
General disorders
Chills	1/20 (5%)	1
Edema limbs	1/20 (5%)	1
Fatigue	15/20 (75%)	27
Fever	1/20 (5%)	1
Gait disturbance	1/20 (5%)	1
Malaise	1/20 (5%)	1
Pain	1/20 (5%)	4
Hepatobiliary disorders
Alanine aminotransferase increased	3/20 (15%)	7
Alkaline phosphatase increased	7/20 (35%)	17
Aspartate aminotransferase increased	4/20 (20%)	14
Blood bilirubin increased	2/20 (10%)	6
Hypoalbuminemia	16/20 (80%)	70
Immune system disorders
Infections and infestations - Other, specify	1/20 (5%)	1
Upper respiratory infection	2/20 (10%)	2
Injury, poisoning and procedural complications
Bruising	2/20 (10%)	2
Metabolism and nutrition disorders
Anorexia	1/20 (5%)	1
Bicarbonate decrease	7/20 (35%)	15
Hypercalcemia	4/20 (20%)	8
Hyperglycemia	17/20 (85%)	92
Hyperkalemia	1/20 (5%)	2
Hypocalcemia	12/20 (60%)	67
Hypokalemia	6/20 (30%)	38
Hypomagnesemia	1/20 (5%)	1
Hyponatremia	8/20 (40%)	54
Hypermagnesemia	2/20 (10%)	7
Musculoskeletal and connective tissue disorders
Back pain	5/20 (25%)	6
Muscle weakness lower limb	1/20 (5%)	1
Pain in extremity	4/20 (20%)	4
Nervous system disorders
Cognitive disturbance	1/20 (5%)	1
Dizziness	6/20 (30%)	6
Headache	3/20 (15%)	4
Neuralgia	1/20 (5%)	1
Peripheral sensory neuropathy	10/20 (50%)	10
Transient ischemic attacks	1/20 (5%)	1
Tremor	1/20 (5%)	1
Psychiatric disorders
Depression	1/20 (5%)	1
Insomnia	4/20 (20%)	4
Psychiatric disorders - Other, specify	1/20 (5%)	1
Renal and urinary disorders
Creatinine increased	12/20 (60%)	102
Renal and urinary disorders - Other, specify	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/20 (15%)	5
Dyspnea	4/20 (20%)	5
Epistaxis	1/20 (5%)	1
Postnasal drip	5/20 (25%)	6
Productive cough	3/20 (15%)	3
Sleep apnea	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/20 (5%)	2
Dry skin	1/20 (5%)	1
Pruritus	1/20 (5%)	1
Rash acneiform	2/20 (10%)	2
Urticaria	1/20 (5%)	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.