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Enzyme Inhibitor

Ibrutinib + Ixazomib for Waldenstrom's Macroglobulinemia

Phase 2
Waitlist Available
Led By Asher A. Chanan-Khan, M.D.
Research Sponsored by Mayo Clinic
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Presence of measurable disease as defined by: presence of immunoglobulin M (IgM) paraprotein, measurable lymphadenopathy on imaging studies and/or physical exam, and/or bone marrow infiltration > 10%
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
Must not have
Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, serious cardiac arrhythmia requiring medication (other than adequately rate-controlled atrial fibrillation), symptomatic congestive heart failure, unstable angina, stroke/transient ischemic attack (TIA) within the past 6 months or myocardial infarction within the past 6 months
Patient has >= grade 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination during the screening period
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 5 years
Awards & highlights
All Individual Drugs Already Approved
Approved for 5 Other Conditions
No Placebo-Only Group

Summary

This trial looks at the side effects of two drugs, ibrutinib and ixazomib, when given together to treat Waldenstrom macroglobulinemia. Enzyme inhibitors, such as ibrutinib and ixazomib, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Who is the study for?
This trial is for adults with Waldenstrom macroglobulinemia, whether newly diagnosed, relapsed or treatment-resistant. Participants must be able to give consent, provide blood and bone marrow samples, have certain minimum blood counts and organ function levels, not be pregnant or breastfeeding, use effective contraception if of childbearing potential, and have no major surgery planned.
What is being tested?
The study tests the effectiveness and side effects of combining two enzyme inhibitors: Ibrutinib citrate and Ixazomib citrate in treating Waldenstrom macroglobulinemia. It includes laboratory biomarker analysis along with pharmacodynamic and pharmacokinetic studies to understand how these drugs work together against cancer cells.
What are the potential side effects?
Potential side effects may include digestive issues due to interference with oral absorption; heart problems like uncontrolled hypertension or arrhythmias; liver dysfunction; nerve pain or neuropathy; increased risk of infection; allergic reactions to medication components; fatigue from anemia or low platelet count.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I have signs of disease like specific proteins in my blood, swollen lymph nodes, or more than 10% of my bone marrow is affected.
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I can take care of myself but might not be able to do heavy physical work.
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My platelet count is at least 75,000 and was tested within the last 14 days without transfusions.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have any uncontrolled heart or blood pressure problems.
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I have moderate to severe nerve damage in my hands or feet, or mild nerve damage with pain.
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I have an active hepatitis B or C infection, or I am HIV positive.
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I am currently being treated with ibrutinib and strong CYP3A inhibitors.
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I haven't had major surgery or a biopsy in the last 14 days and don't expect to need one soon.
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I haven't had any cancer treatment or joined other clinical trials in the last 28 days.
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I am currently breastfeeding.
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I don't have GI issues that affect medicine absorption.
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My condition involves the central nervous system.
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My liver is not working well (Child-Pugh B or C).

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 5 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Complete response rate (CR)
Secondary study objectives
Incidence of adverse effects (AE) graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0
Overall response rate
Overall survival
+1 more
Other study objectives
BTK signaling proteins (western blot and densitometric quantification) and gene expression (quantitative real-time polymerase chain reaction [PCR]) examined in CD19/CD138+ Waldenstrom macroglobulinemia (WM) cells
Biologic effects of ibrutinib and ixazomib citrate on microenvironment in WM

Side effects data

From 2024 Phase 2 trial • 18 Patients • NCT03370718
78%
Alanine aminotransferase increased
78%
Diarrhea
72%
Aspartate aminotransferase increased
72%
White blood cell decreased
67%
Weight loss
67%
Hypertension
61%
Alkaline phosphatase increased
56%
Fatigue
50%
Hypophosphatemia
50%
Nausea
50%
Proteinuria
44%
Increased TSH
44%
Lipase increased
44%
Palmar-plantar erythrodysesthesia syndrome
44%
Dysgeusia
39%
Platelet count decreased
39%
Creatinine increased
39%
Increased amylase
39%
Increased GGT
39%
Abdominal pain
39%
Anemia
39%
Increased LDH
33%
Blood bilirubin increased
33%
Mucositis oral
33%
Anorexia
33%
Dry skin
33%
Hyperglycemia
33%
Vomiting
33%
Hypoalbuminemia
28%
Erythema/Rash
28%
Hypokalemia
28%
Hypomagnesemia
28%
Headache
28%
Skin hypopigmentation
22%
Insomnia
22%
Constipation
22%
Muscle cramps
22%
Hair color changing
17%
Dyspnea
17%
Muscle weakness
17%
Back pain
17%
Hypercalcemia
17%
Hoarseness
17%
Paresthesia
17%
Hypothyroidism
17%
Thromboembolic event
11%
Dyspepsia
11%
Dizziness
11%
Dry mouth
11%
Heat intolerance
11%
Increased calluses on feet
11%
Lightheadedness
11%
Sinus tachycardia
11%
Sore throat
11%
Voice change
11%
GGT increased
11%
Increased PTT
11%
Bruising
11%
Extremity pain
11%
Flank pain
11%
Hyponatremia
11%
Myalgia
11%
Oral hemorrhage
11%
Pleural effusion
11%
Free T4 alteration
11%
Stomatitis
6%
Renal Insufficiency
6%
Skin infection
6%
Syncope
6%
Tremor
6%
Weight gain
6%
Cough
6%
Dysphagia
6%
Decreased Chloride
6%
Hand pain/ joint stiffness
6%
Hematemesis
6%
Hyperkalemia
6%
Increased BUN
6%
INR increased
6%
Intracranial hemorrhage
6%
Itching
6%
Melanoma In Situ
6%
Nasal discharge
6%
Oral pain
6%
Pneumothorax
6%
Sinus bradycardia
6%
Slow growth of hair
6%
Total Protein decreased
6%
Tumor pain
6%
Urinary tract pain
6%
Nasal congestion
6%
Skin hyperpigmentation
6%
Gait disturbance
6%
Increased Total Protein
6%
Ureteral obstruction
6%
Increased PT
6%
Acne
6%
Belching
6%
Cholecystitis
6%
Acute respiratory failure
6%
Arthralgia
6%
Chronic kidney disease
6%
Cortisol increase
6%
Edema
6%
Epistaxis
6%
Facial pain
6%
Gingival pain
6%
Hair loss
6%
Hemorrhoidal hemorrhage
6%
Hydronephrosis
6%
Hypocalcemia
6%
Increased Globulin
6%
Increased skin sensitivity
6%
Increased T4
6%
Irregular menstruation
6%
Loss of Peripheral vision
6%
Odynophagia
6%
Osteonecrosis of jaw
6%
Pallor
6%
Pancreatitis
6%
Peeling and Dry blistering
6%
Pneumonia bibasilar
6%
Sinus disorder
6%
Soreness on sole of feet
6%
Urinary hesitancy
6%
Thyrotoxicosis
6%
Radiculitis
100%
80%
60%
40%
20%
0%
Study treatment Arm
Cabozantinib

Awards & Highlights

All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.
Approved for 5 Other Conditions
This treatment demonstrated efficacy for 5 other conditions.
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups
Experimental Treatment
Group I: Treatment (ixazomib citrate, ibrutinib)Experimental Treatment5 Interventions
Patients receive ixazomib citrate PO on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Ixazomib
FDA approved
Ibrutinib
FDA approved

Find a Location

Who is running the clinical trial?

Mayo ClinicLead Sponsor
3,362 Previous Clinical Trials
3,065,937 Total Patients Enrolled
12 Trials studying Waldenstrom Macroglobulinemia
539 Patients Enrolled for Waldenstrom Macroglobulinemia
National Cancer Institute (NCI)NIH
13,957 Previous Clinical Trials
41,112,063 Total Patients Enrolled
137 Trials studying Waldenstrom Macroglobulinemia
8,459 Patients Enrolled for Waldenstrom Macroglobulinemia
Asher A. Chanan-Khan, M.D.Principal InvestigatorMayo Clinic
Asher A Chanan-KhanPrincipal InvestigatorMayo Clinic

Media Library

Ibrutinib (Enzyme Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03506373 — Phase 2
Waldenstrom Macroglobulinemia Research Study Groups: Treatment (ixazomib citrate, ibrutinib)
Waldenstrom Macroglobulinemia Clinical Trial 2023: Ibrutinib Highlights & Side Effects. Trial Name: NCT03506373 — Phase 2
Ibrutinib (Enzyme Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03506373 — Phase 2
~1 spots leftby May 2025