Clinical Trials /

Ixazomib + Pomalidomide + Dexamethasone In MM

NCT04094961

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib + Pomalidomide + Dexamethasone In MM
  • Official Title: Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed/or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 19-291
  • NCT ID: NCT04094961

Conditions

  • Multiple Myeloma
  • Multiple Myeloma in Relapse

Interventions

DrugSynonymsArms
IxazomibNinlaro®ixazomib plus pomalidomide and dexamethasone
PomalidomidePomalyst®ixazomib plus pomalidomide and dexamethasone
DexamethasoneBaycadron, Decadron, Dexamethasone Intensol, DexPak, TaperDex, Zema-Pak, ZoDex, Zonacortixazomib plus pomalidomide and dexamethasone

Purpose

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.

Detailed Description

      This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an
      investigational drug and tries to define the appropriate dose of the investigational drug to
      use for further studies. "Investigational" means that the drug is being studied.

      The FDA has approved both pomalidomide and ixazomib individually for the treatment of
      multiple myeloma. Dexamethasone, also FDA approved, is a type of steroid and is usually
      combined with other chemotherapy for the treatment of blood cancers, such as myeloma and
      leukemias.

        -  Ixazomib targets a part of cells called proteasomes. It works by slowing down or
           blocking proteasomes from doing their job of digesting proteins. In myeloma cells, there
           is a greater need for proteasomes to digest proteins; the buildup of excess proteins
           causes cell death.

        -  Pomalidomide has also been shown to cause tumor cell deaths. Dexamethasone can stop
           white blood cells from traveling to areas myeloma cells are causing damage. When
           combined with myeloma drugs, it sometimes makes those drugs work better.

      In this research study, the investigators are:

        -  Testing the safety of ixazomib when given with pomalidomide and dexamethasone

        -  Pomalidomide and ixazomib are given individually for the treatment of multiple myeloma.
           Dexamethasone is also given for multiple myeloma

        -  Ixazomib when combined with pomalidomide and dexamethasone may help control the disease

        -  Ixazomib is FDA approved to treat multiple myeloma

        -  The investigators are looking for the highest dose of ixazomib that can be given safely
           in combination with pomalidomide and dexamethasone
    

Trial Arms

NameTypeDescriptionInterventions
ixazomib plus pomalidomide and dexamethasoneExperimentalThe 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
  • Ixazomib
  • Pomalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  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

                    -  Calculated creatinine clearance ≥ 45 mL/min

               -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

               -  All study participants must be registered into the mandatory POMALYST REMS®
                  program, and be willing and able to comply with the requirements of the POMALYST
                  REMS® program.

               -  Females of reproductive potential must adhere to the scheduled pregnancy testing
                  as required in the POMALYST REMS® program.

               -  Ability to understand and the willingness to sign a written informed consent
                  document.

        Exclusion Criteria:

          -  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.

               -  Prior allogeneic stem cell transplantation with active graft-versus-host-disease.

          -  Currently active graft versus host disease of any stage or grade after allogeneic stem
             cell transplantation

          -  Prior major surgical procedure or radiation therapy within 14 days of initiation of
             therapy.

               -  Those who require a limited course of radiation for management of bone pain more
                  than 14 days out from initiation of therapy are not excluded

               -  If the involved field is small, 7 days will be considered a sufficient interval
                  between radiotherapy and administration of the ixazomib.

          -  Daily requirement for corticosteroids (equivalent to > 10 mg/day prednisone, though
             >10mg/day is acceptable if physiological levels require, so long as the dose is stable
             for at least 7 days prior to initiation of therapy. Inhalation corticosteroids are
             exempt from this criterion.

             -- Lower amounts of corticosteroids that are not part of a daily requirement within 14
             days prior to initiating therapy

          -  Concurrent symptomatic amyloidosis or plasma cell leukemia

          -  POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein and skin changes)

          -  Infection requiring systemic antibiotic therapy or other serious infection within 14
             days before study enrollment.

             -- Those who are on prophylactic antibiotics only, or on antibiotics and have
             confirmation of resolution of active infection are eligible.

          -  Known seropositive for active viral infection with human immunodeficiency virus (HIV)
             hepatitis B (HBV) or hepatitis C viral (HCV). Those who are seropositive because of
             hepatitis B vaccine are eligible. Patients who are positive for HBV core antibody or
             HBV surface antigen must have a negative polymerase chain reaction (PCR) result prior
             to enrollment. Those who are PCR positive will be excluded

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period

          -  Participants who are receiving any other investigational agents for any indication

          -  History of erythema multiforme or severe hypersensitivity to prior IMiD's® or those
             who have a known allergy to any of the study medications, their analogues, or
             excipients in the various formulations of any agent.

          -  Inability to tolerate thromboprophylaxis

          -  Failure to have fully recovered (≤ Grade 1 according to CTCAE v 5) from the reversible
             effects of prior chemotherapy

          -  Peripheral neuropathy must have resolved to Grade 1 toxicity or peripheral neuropathy
             grade 2 with no pain to be eligible

          -  Alopecia of any grade is eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose limiting toxicity
Time Frame:21 Days
Safety Issue:
Description:3 - 24 safety evaluable patients will be enrolled in up to 4 dose levels of ixazomib, pomalidomide and dexamethasone.

Secondary Outcome Measures

Measure:Time to Progression
Time Frame: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
Safety Issue:
Description:Estimated using the method of Kaplan-Meier.
Measure:Progression Free Survival
Time Frame: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
Safety Issue:
Description:Estimated using the method of Kaplan-Meier.
Measure:Duration of Response
Time Frame: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
Safety Issue:
Description:Estimated using the method of Kaplan-Meier.
Measure:Overall Survival
Time Frame:time from first dose of study drug to death or date last known alive, whichever came first, assessed up to 60 months
Safety Issue:
Description:Estimated using the method of Kaplan-Meier.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Paul G. Richardson, MD

Trial Keywords

  • Multiple Myeloma
  • Multiple Myeloma in Relapse

Last Updated

January 29, 2020