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MyelomaPhase 1/2NCT02542657

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

A Phase 1/2 study testing Clarithromycin, Dexamethasone and Ixazomib Citrate in people with Myeloma, run by Joseph Tuscano at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myeloma
What is being tested?
Clarithromycin, Dexamethasone and Ixazomib Citrate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
3 sitesUnited States
Study dates
22 Oct 2015to 11 Nov 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Hypercalcemia (corrected serum calcium > 11.5 mg/dL) attributable to myeloma (e.g. not due to omitted doses of bisphosphonate)
  • Life expectancy of greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
  • Disease free of prior malignancies for > 5 years with exception of patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 and
  • Platelet count >= 50,000/mm^3; note: platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
  • Total bilirubin =< 2.0 × the upper limit of the normal range (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 × ULN
  • Calculated creatinine clearance >= 30 mL/min
  • 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 two 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, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Male patients, even if surgically sterilized (i.e., 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 [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)

Who cannot join

  • 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
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  • 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
  • Cluster of differentiation (CD)4+ cells nadirs > 350/mm^3
  • Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3; please note: HIV+ patients who enroll on this study may need to modify their anti-retroviral therapy prior to receiving protocol therapy if they are on strong inducers or potent inhibitors of cytochrome P450; adverse events in HIV+ patients will be reported separately
  • 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
  • Previous allergic reaction to an immunomodulatory drug (IMiD)
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drugs including difficulty swallowing
  • Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
  • Previous treatment with ixazomib or pomalidomide

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of California San Diego

    La Jolla, California, 92093-0960

  • University of California Irvine

    Orange, California, 92868

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase I/II Study of Ixazomib in Combination With Pomalidomide, Clarithromycin and Dexamethasone (PiC-D) in Patients With Double Refractory Multiple Myeloma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) for PiC-D therapy (pomalidomide, ixazomib [ixazomib citrate], clarithromycin, and dexamethasone) in patients with multiple myeloma who are bortezomib and lenalidomide refractory. (Phase I) II. To determine the complete response (CR) and stringent CR (sCR) rate for PiC-D therapy in patients with multiple myeloma who are bortezomib and lenalidomide refractory. (Phase II)

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of PiC-D therapy. (Phase I) II. To characterize the pharmacokinetics (PK) in plasma of oral ixazomib in combination with pomalidomide, clarithromycin and dexamethasone. (Phase I) III. To assess preliminary evidence of clinical activity. (Phase I) IV. To assess the effects of PiC-D therapy on quality of life (QOL). (Phase I)

VI. To evaluate the safety of PiC-D therapy. (Phase II) VII. To determine the overall response rate (ORR) (ORR; CR, sCR, partial response, and very good partial response. (Phase II) VIII. To determine the clinical benefit rate (CBR) (CBR; minimal response + ORR). (Phase II) IX. To determine the disease control rate (DCR) (DCR; stable disease + CBR). (Phase II) X. To determine the duration of response (DOR) in patients achieving a partial response or better. (Phase II) XI. To determine the time to next treatment (TNT). (Phase II) XII. To determine progression free survival (PFS) and overall survival (OS). (Phase II)

OUTLINE: This is a phase I, dose-escalation study of clarithromycin followed by a phase II study.

Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21; ixazomib citrate PO on days 1, 8, and 15; clarithromycin PO twice daily (BID) on days 15-21 of course 1 and days 1-21 and 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.

After completion of study treatment, patients are followed up every 2-3 months for up to 3 years.

Conditions
Myeloma
Being tested
Clarithromycin, Dexamethasone, Ixazomib Citrate, Pomalidomide
Medical subject headings
Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02542657
Study groupRoleWhat they receive
Treatment (PiC-D therapy)ExperimentalPatients 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.
Receives: Drug: Clarithromycin; Drug: Dexamethasone; Drug: Ixazomib Citrate; Drug: Pomalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) (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. Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: About 14 months.

  2. Complete Response (CR) and Stringent CR (Phase 2)

    Defined by the International Myeloma Working Group (IMWG) criteria. omplete response (CR) = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. Stringent complete response (sCR) = CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence>

    Measured: Up to about 7 years

Secondary outcomes (12)

  1. Safety and Tolerability of PiC-D Therapy (Phase 1)

    Proportion of patients experiencing dose limiting toxciity (DLT).

    Measured: Up to about 14 months

  2. Preliminary Evidence of Clinical Activity (Phase 1).

    SD (stable disease), VGPR (very good partial response), sCR (stringent complete response), overall response rate (ORR), CBR (clinical benefit rate), and DCR (disease control rate).

    Measured: Up to 3 years

  3. Quality of Life (Phase 1)

    Cancer Therapy Satisfaction Questionnaire and EORTC QLQ-MY20 score.

    Measured: Up to 2 years

  4. Safety (Phase 2)

    Proportion of patients experiencing treatment-emergent adverse events, graded according to CTCAE v4.03.

    Measured: Up to about 2.5 years

  5. Overall Response Rate (ORR) (Phase 2)

    ORR = PR+VGPR+CR. Overall response rate (ORR) includes Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR). Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria

    Measured: Up to about 7 years

  6. Clinical Benefit Rate (CBR) (Phase 2)

    CBR = Number of participants with Minimal Response (MR) or better, defined as sCR (Stringent Complete Response) + CR (Complete Response) + VGPR (Very Good Partial Response) + PR (Partial Response) + MR (Minimal Response).

    Measured: Up to 3 years

  7. Disease Control Rate (DCR) (Phase 2)

    Disease control rate (DCR) = stable disease (SD) + overall response rate (ORR)

    Measured: Up to about 7 years

  8. Duration of Response (DOR) (Phase 2)

    DOR = Partial response (PR) or better. PR defined per IMWG as ≥ 50% reduction of serum M-protein and reduction in 24 h urinary M-protein by ≥ 90% or to < 200 smg per 24 h.

    If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥ 50% reduction in plasma cells is required in place of the M-protein, provided baseline bone marrow plasma cell percentage was ≥ 30% In addition to the above listed criteria, if present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

    Measured: Up to about 7 years

  9. Progression Free Survival (PFS) (Phase 2)

    Median progression free survival (PFS) - Median time from initiation of study intervention to progressive disease (PD) per IMWG criteria.

    Measured: Up to 3 years

  10. Overall Survival (OS) (Phase 2)

    Median time from initiation of study intervention to death from any cause

    Measured: Up to about 6 years

  11. Quality of Life (QoL) (Phase 2)

    Cancer Therapy Satisfaction Questionnaire (CTSQ-16) - Perceived worth of therapy, taken at screening and at end of treatment.

    Measured: Baseline and end of treatment (up to 3 years).

  12. Phamacokinetic Parameters of Ixazomib Citrate

    Data not collected

    Measured: at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after ixazomib citrate administration on days 1 and 8.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2015 (estimated)
  2. Study start22 Oct 2015
  3. Primary completion7 Dec 2022
  4. Study completion11 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02542657
Sponsor's protocol ID
728937
Other IDs
UCDCC#253, X16043, UCDCC#253, PO-TR-MM-PI-004614
Status last verified
Oct 2026
First submitted
8 May 2015
Last updated
2 Nov 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40948663

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Clarithromycin, Dexamethasone and Ixazomib Citrate in people with Myeloma, run by Joseph Tuscano at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (Phase I) (time frame: About 14 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02542657, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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