Clinical Trials /

Ixazomib Citrate, Pomalidomide, Dexamethasone, and Stem Cell Transplantation in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT03202628

Description:

This phase II trial studies how well ixazomib citrate, pomalidomide, dexamethasone, and stem cell transplantation works in treating patients with multiple myeloma that has come back or does not respond to treatment. Giving chemotherapy, such as pomalidomide and dexamethasone, before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving ixazomib citrate in addition to pomalidomide, dexamethasone, and stem cell transplantation may work better in treating patients with relapsed or refractory multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib Citrate, Pomalidomide, Dexamethasone, and Stem Cell Transplantation in Treating Patients With Relapsed or Refractory Multiple Myeloma
  • Official Title: Phase 2 Trial of Induction With Ixazomib, Pomalidomide, Dexamethasone Prior to Salvage Autologous Stem Cell Transplantation Followed by Consolidation With Ixazomib, Pomalidomide, and Dexamethasone and Ixazomib Maintenance in Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: MC168A
  • SECONDARY ID: NCI-2017-01145
  • SECONDARY ID: MC168A
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03202628

Conditions

  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma

Interventions

DrugSynonymsArms
DexamethasoneAacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, VisumetazoneTreatment (ixazomib, pomalidomide, dexamethasone, ASCT)
Ixazomib CitrateMLN-9708, MLN9708, NinlaroTreatment (ixazomib, pomalidomide, dexamethasone, ASCT)
Pomalidomide4-Aminothalidomide, Actimid, CC-4047, Imnovid, PomalystTreatment (ixazomib, pomalidomide, dexamethasone, ASCT)

Purpose

This phase II trial studies how well ixazomib citrate, pomalidomide, dexamethasone, and stem cell transplantation works in treating patients with multiple myeloma that has come back or does not respond to treatment. Giving chemotherapy, such as pomalidomide and dexamethasone, before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving ixazomib citrate in addition to pomalidomide, dexamethasone, and stem cell transplantation may work better in treating patients with relapsed or refractory multiple myeloma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the rate of progression free survival at 18 months from study entry after
      therapy with ixazomib citrate (ixazomib [MLN9708]) in combination with pomalidomide and
      dexamethasone followed by a single autologous stem cell transplantation (ASCT) and
      consolidation with ixazomib in combination with pomalidomide and dexamethasone and
      maintenance with ixazomib in relapsed refractory ASCT naive multiple myeloma (MM) patients.

      SECONDARY OBJECTIVES:

      I. To determine the best overall response rates (>= partial response [PR]) and deep responses
      (very good partial response [VGPR], complete response [CR], stringent complete response
      [sCR]) at various stages of treatment: after induction, after stem cell transplantation
      (SCT), after consolidation and during maintenance.

      II. To determine the overall survival from study entry.

      TERTIARY OBJECTIVES:

      I. Assessment of minimal residual disease (MRD) by flow cytometry at various stages of
      treatment: after induction, day # 100 after SCT, after consolidation and during maintenance
      at year 1 and 2 from initiation of maintenance therapy.

      II. To determine the engraftment kinetics (white blood cells [WBC] and platelet) following
      single salvage ASCT for relapsed disease.

      OUTLINE:

      INDUCTION (COURSES 1-4): Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15,
      pomalidomide (PO) on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment
      repeats every 28 days (courses 1-3) and 56 days (course 4) for up to 4 courses in the absence
      of disease progression or unacceptable toxicity.

      TRANSPLANTATION (COURSE 5): Between 2-4 weeks following Induction, patients undergo ASCT.

      CONSOLIDATION (COURSES 6-9): Beginning 60-120 days following ASCT, patients receive ixazomib
      citrate, pomalidomide, and dexamethasone as in Induction. Treatment repeats every 28 days
      (courses 6-8) and 56 days (course 9) for up to 4 courses in the absence of disease
      progression or unacceptable toxicity.

      MAINTENANCE (COURSES 10+): Beginning 0-4 weeks following Consolidation, patients receive
      ixazomib citrate as in Induction. Courses repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months until
      progressive disease, and then every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)ExperimentalINDUCTION (COURSES 1-4): Patients receive ixazomib citrate PO on days 1, 8, and 15, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days (courses 1-3) and 56 days (course 4) for up to 4 courses in the absence of disease progression or unacceptable toxicity. TRANSPLANTATION (COURSE 5): Between 2-4 weeks following Induction, patients undergo ASCT. CONSOLIDATION (COURSES 6-9): Beginning 60-120 days following ASCT, patients receive ixazomib citrate, pomalidomide, and dexamethasone as in Induction. Treatment repeats every 28 days (courses 6-8) and 56 days (course 9) for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE (COURSES 10+): Beginning 0-4 weeks following Consolidation, patients receive ixazomib citrate as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Dexamethasone
  • Ixazomib Citrate
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Previously treated ASCT naive MM patients, currently with relapsed or refractory
             disease who are being considered for single ASCT for relapsed disease; patients must
             be eligible to undergo a stem cell transplant as per institutional criteria for
             selection at the time of registration

          -  Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min

          -  Absolute neutrophil count (ANC) >= 1000/mm^3

          -  Platelet count >= 75 x 10^9/L unless the participant has >= 50% bone marrow
             infiltration in which case a platelet count of >= 50 x 10^9/L is allowed

          -  Hemoglobin >= 9.0 g/dL

          -  Total bilirubin =< 1.5 x the upper limit of the normal range (ULN) or if total
             bilirubin is > 1.5 x ULN, the direct bilirubin must be =< 2.0 mg/dL

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN or < 5
             x ULN if liver involvement

          -  Patients with measurable disease defined as at least one of the following:

               -  Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis

               -  >= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis

               -  Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
                  immunoglobulin kappa to lambda free light chain ratio

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Willing to provide informed written consent

          -  Negative pregnancy test done =< 7 days prior to registration, for persons of
             childbearing potential only

          -  Willing to follow strict birth control measures

          -  Persons of childbearing potential, agree to one of the following:

               -  Practice 2 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, AND must also adhere to the guidelines of any treatment-specific pregnancy
                  prevention program, if applicable, 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)

          -  Persons able to father a child: 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

               -  Must also adhere to the guidelines of any treatment-specific pregnancy prevention
                  program, if applicable, 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)

          -  Willing to follow the requirements of the Pomalyst REMS program

          -  Willing to return to return to enrolling institution for follow-up (during the Active
             Monitoring Phase of the study)

          -  Willing to provide bone marrow samples under Institutional Review Board (IRB)#521-93
             for correlative research purposes

        Exclusion Criteria:

          -  Diagnosed or treated for another malignancy =< 2 years prior to registration or
             previously diagnosed with another malignancy and have any evidence of residual disease

               -  NOTE: If there is a history or prior malignancy, patient must not be receiving
                  other specific treatment for their cancer; patients with non-melanoma skin cancer
                  or carcinoma in situ of any type, or low-risk prostate cancer after curative
                  therapy, are not excluded if they have undergone complete resection

               -  NOTE: Platelet transfusions to help patients meet eligibility criteria are not
                  allowed =< 3 days prior to study registration

          -  Any of the following:

               -  Pregnant persons

               -  Nursing persons

               -  Persons of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens; NOTE: this includes uncompensated heart or lung disease

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm; NOTE: Bisphosphonates are considered to be supportive care
             rather than therapy and are allowed while on protocol treatment

          -  Patient has >= grade 2 peripheral neuropathy, or grade 1 with pain on clinical
             examination during the screening period

          -  Major surgery =<14 days prior to registration

          -  Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,
             carbamazepine, phenytoin, phenobarbital) or use of Ginkgo biloba or St. John?s wort =<
             14 days prior to registration

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements. NOTE: Any electrocardiogram (ECG) abnormality at screening must be
             documented by the investigator as not medically relevant

          -  Corrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the
             screening period; Note: If a machine reading is above this value, the ECG should be
             reviewed by a qualified reader and confirmed on a subsequent ECG

          -  Known human immunodeficiency virus (HIV) positive

          -  Known hepatitis B surface antigen-positive status, or known or suspected active
             hepatitis C infection

          -  Known allergy to any of the study medications, their analogues or excipients in the
             various formulations

          -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of study treatment including difficulty swallowing

          -  Diarrhea > grade 1, based on the National Cancer Institute (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE) version (v) 4.0 grading, in the absence of
             antidiarrheals

          -  Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible
             effects of prior chemotherapy

          -  Radiotherapy =< 14 days prior to registration; NOTE: If the involved field is small, 7
             days will be considered a sufficient interval between treatment and administration of
             the ixazomib

          -  Central nervous system involvement with disease under study (myeloma), or concurrent
             AL amyloidosis or plasma cell leukemia

          -  Patients that have previously been treated with ixazomib, or participated in a study
             with ixazomib whether treated with ixazomib or not

          -  Prior stem cell transplantation for myeloma
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival at 18 months (PFS18) defined as the proportion of patients alive and free from disease progression at 18 months from study entry
Time Frame:At 18 months
Safety Issue:
Description:The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. If patients are censored prior to 18 months post registration, a Kaplan Meier (Kaplan, E. and Meier, P., 1958) estimate for PFS18 along with the 95% confidence intervals will be reported.

Secondary Outcome Measures

Measure:Greater than or equal to (>=) very good partial response (VGPR) rate
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated by the number of patients who achieve a stringent complete response (sCR), complete response CR, or VGPR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall >= VGPR will be calculated.
Measure:Incidence of adverse events graded according to the National Cancer Institute (NC) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4
Time Frame:Up to 3 years
Safety Issue:
Description:The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Measure:Overall response rate
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated by the number of patients who achieve a stringent complete response (sCR), complete response CR, very good partial response (VGPR), or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Measure:Overall survival
Time Frame:From registration to the last date of documentation of follow-up or death due to any cause, assessed for up to 3 years
Safety Issue:
Description:The distribution of overall survival will be estimated using the method of Kaplan-Meier.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

August 30, 2019