Ixazomib + Pomalidomide + Dexamethasone In MM

NCT04094961 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-291
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II study using the combination of twice weekly ixazomib plus pomalidomide and dexamethasone in relapsed and or refractory multiple myeloma (RRMM) patients.

Conditions

Multiple Myeloma; Multiple Myeloma in Relapse

Keywords

Multiple Myeloma; Multiple Myeloma in Relapse

Outcome Measures

Primary Outcomes (2)

• Number of participants with dose limiting toxicity

  3 - 24 safety evaluable patients will be enrolled in up to 4 dose levels of ixazomib, pomalidomide and dexamethasone.

  21 Days

• Overall Response Rate

  Response will be evaluated using a Simon optimal two-stage design

  28 days

Secondary Outcomes (4)

• Time to Progression

  time from first dose of study drug to progression, censored at date last known progression-free for those who have not progressed, whichever came first, assessed up to 60 months

• Progression Free Survival

  time from first dose of study drug to the disease progression or death from any cause, censored at date last known progression-free for those who have not progressed or died, whichever came first, assessed up to 60 months

• Duration of Response

  time from response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died, whichever came first, assessed up to 60 months

• Overall Survival

  time from first dose of study drug to death or date last known alive, whichever came first, assessed up to 60 months

Study Arms (1)

ixazomib plus pomalidomide and dexamethasone

EXPERIMENTAL

The study drugs will be administered within a 21-day cycle * Phase I will follow a standard "3 +3" dose escalation design: Starting with the first cohort, 3 to 6 patients will be treated at this and each subsequent dose level. * The Phase II portion of the study will be a single-arm open-label enrollment with dosing based on the MTD determination in the Phase I portion of the study

Drug: Ixazomib; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Oral, administered four times per cycle

Also known as: Ninlaro®

ixazomib plus pomalidomide and dexamethasone

Pomalidomide DRUG

Oral, administered 14 times per cycle

Also known as: Pomalyst®

ixazomib plus pomalidomide and dexamethasone

Dexamethasone DRUG

Oral, fixed dose administered 8 times per cycle

Also known as: Baycadron, Decadron, Dexamethasone Intensol, DexPak, TaperDex, Zema-Pak, ZoDex, Zonacort

ixazomib plus pomalidomide and dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patients with relapsed and relapsed refractory myeloma may be eligible for this trial of they meet all the following entry criteria.
• Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.
• Patient has given voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
• Patient had received at least two previous therapies OR received 1 prior line of therapy if previously treated with an IMiD plus a proteasome inhibitor and has demonstrated disease progression on or within 60 days of completion of the last therapy
• Patient has measurable disease defined as at least one of the following according to Standard Diagnostic Criteria (Rajkumar 2014):
• Serum IgG, IgA, or IgM M-protein ≥ 0.5 g/dL, or
• Serum IgD M-protein ≥ 0.05 g/dL, or
• Urine M protein ≥200 mg/24 hours or
• Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65)
• Screening Laboratory evaluations within the following parameters
• Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used more recently than 14 days prior to initiation of therapy)
• Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions required during the 14 days prior to initiation of therapy)
• Hemoglobin ≥ 8.0 g/dl (RBC transfusions are permitted)
• Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN

You may not qualify if:

• Prior exposure to ixazomib OR is refractory to pomalidomide
• Patients that have previously been treated with ixazomib, or participated in a study with ixazomib,whether treated with the agent or not, are also excluded
• 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.
• Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
• Known GI disease or is in need of, or has had a previous GI procedure that could interfere with the oral absorption or tolerance of ixazomib or pomalidomide including difficulty swallowing.
• Known central nervous system involvement.
• Systemic treatment, within 14 days before the first dose of treatment, with strong CYP3A or inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort OR systemic treatment within 14 days of the first dose of treatment with a strong inhibitor of CYP1A2 (ciprofloxacin, fluvoxamine, cimetidine, enoxacin, ethynyl estradiol, mexiletine)
• Any medical or psychiatric illness/social situation that in the Investigator's opinion, would impose excessive risk to the patient, would adversely affect his/her participating in this study or would limit compliance with study requirements.
• Any active, or uncontrolled cardiovascular conditions, including but not limited to uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, grade 3 thromboembolic event or myocardial infarction within the past 6 months.
• The following therapies within the stated time frames prior to initiation of therapy:
• Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 21 days (42 days for nitrosoureas).
• The use of live vaccines within 30 days.
• ImiDs or proteasome inhibitors within 14 days.
• Other investigational therapies and/or monoclonal antibodies within 4 weeks.
• Prior peripheral stem cell transplant within 12 weeks.

Sponsors & Collaborators

• Omar Nadeem, MD: lead
• Takeda: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; pomalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Omar Nadeem, MD

  Dana-Farber Cancer Institute

  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: September 10, 2019
• First Posted: September 19, 2019
• Study Start: September 18, 2019
• Primary Completion: June 1, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)