Ixazomib with Pomalidomide, Clarithromycin and Dexamethasone in Treating Patients with Multiple Myeloma

NCT02542657 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 728937UCDCC#253X16043PO-TR-MM-PI-004614
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/II trial studies the side effects and best dose of clarithromycin when given together with ixazomib citrate, pomalidomide, and dexamethasone and to see how well it works in treating patients with multiple myeloma that has not responded to previous treatment. Biological therapies, such as clarithromycin, pomalidomide, and dexamethasone, use substances made from living organisms that may stimulate the immune system in different ways and stop cancer cells from growing. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving clarithromycin with ixazomib citrate, pomalidomide and dexamethasone may be a better treatment for patients with multiple myeloma.

Conditions

Myeloma

Outcome Measures

Primary Outcomes (1)

• MTD of clarithromycin when given in combination with ixazomib citrate, pomalidomide, and dexamethasone assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

  The MTD is defined as the highest dose tested in which fewer than 33% of patients experience a dose limiting toxicity and at least 6 patients have been treated at that dose. The MTD will be the recommended Phase 2 dose, provided that other safety considerations are acceptable.

  28 days

Secondary Outcomes (1)

• Clinical best response

  Up to 3 years

Other Outcomes (3)

• Change in immune modulation with the addition of clarithromycin (Phase II)

  Up to 3 years

• Change in immune modulation without the addition of clarithromycin (Phase II)

  Baseline to up to 3 years

• Pharmacokinetic parameters of ixazomib citrate (Individual and mean plasma ixazomib concentration data)

  At 0.5, 1, 1.5, 2, 4, 8, and 24 hours after ixazomib citrate administration on days 1 and 8

Study Arms (1)

Treatment (PiC-D therapy)

EXPERIMENTAL

Patients receive pomalidomide PO QD on days 1-21; ixazomib citrate PO on days 1, 8, and 15; clarithromycin PO BID on days 15-21 of course 1 and days 1-21 of courses 2-6; and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pomalidomide, ixazomib citrate, and dexamethasone as above and receive clarithromycin PO BID or QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Clarithromycin; Drug: Dexamethasone; Drug: Ixazomib Citrate; Drug: Pomalidomide

Interventions

Clarithromycin DRUG

Given PO

Also known as: Biaxin

Treatment (PiC-D therapy)

Dexamethasone DRUG

Given PO

Also known as: Decadron

Treatment (PiC-D therapy)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN9708

Treatment (PiC-D therapy)

Pomalidomide DRUG

Given PO

Also known as: Pomalyst

Treatment (PiC-D therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written consent
• Patients must have a confirmed biopsy diagnosis of a multiple myeloma
• Submission of original biopsy for review and verification by hematopathologist at local institution
• Patients must have measurable disease according to International Myeloma Working Group (IMWG) criteria; measurable disease includes at least one of the following criteria:
• Serum M-protein \>= 1.0 g/dL, and/or
• Urine M-protein \>= 200 mg/24 hours, and/or
• Involved serum free light chain \>= 10 mg/dL (\>= 100 mg/L) AND an abnormal serum free light chain ratio, and/or
• Baseline marrow burden or myeloma of at least 30%
• Disease that has progressed during or within 6 months of coming off therapy with bortezomib and lenalidomide (either sequentially or concurrent); progressive disease is defined as any of the following:
• An increase of \>= 25% from lowest response value in any of the following:
• Serum M-protein (absolute increase must be \>= 0.5 g/dL) AND/OR
• Urine M-protein (absolute increase must be \>= 200 mg/24 hours) AND/OR
• For patients without a measurable serum or urine M-protein but measurable disease by serum free light chain testing: Difference between the involved and uninvolved serum free light chain level (absolute increase must be \>= 10 mg/dL) AND/OR
• For patients without a measurable serum or urine M-component or serum free light chain level: % marrow involvement with myeloma (absolute increase must be \>= 10%) AND/OR
• Definite development of new bone lesions or extramedullary plasmacytomas or definite increase in the size of existing bone lesions or extramedullary plasmacytomas AND/OR

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Treatment with clarithromycin, anti-myeloma therapy including investigational agents or plasmapheresis within 30 days prior to treatment in this study
• Failure to have fully recovered (i.e., =\< grade 1 toxicity or to patient's clinical baseline) from the reversible effects of prior chemotherapy
• Major surgery within 14 days before enrollment
• Radiotherapy 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 of study drugs, or concurrent use, with any of the following:
• Strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2)
• Strong inhibitors of family cytochrome P450 family 3, subfamily A (3A)
• Strong cytochrome 3A polypeptide 4 inducers
• Known ongoing or active systemic infection, active hepatitis B or C virus infection
• Patients with human immunodeficiency virus (HIV) infection may be eligible provided they meet the following:
• No history of acquired immunodeficiency syndrome (AIDS)-defining conditions or other HIV related illness

Sponsors & Collaborators

• Joseph Tuscano: lead
• Takeda: collaborator
• Celgene: collaborator

Study Sites (3)

University of California San Diego

La Jolla, California, 92093-0960, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

• Rosenberg AS, Maverakis E, Costello C, Brem EA, Wieduwilt MJ, Luxardi G, Kaesberg P, Abedi K, Herbert S, Tuscano J. Clarithromycin, ixazomib, pomalidomide, dexamethasone for relapsed/refractory myeloma: survival and correlative analysis. Blood Neoplasia. 2025 Jan 16;2(3):100067. doi: 10.1016/j.bneo.2025.100067. eCollection 2025 Aug.

  PMID: 40948663 DERIVED

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

Clarithromycin; Dexamethasone; Calcium Dobesilate; ixazomib; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Joseph Tuscano

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: September 7, 2015
• Study Start: October 1, 2015
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)