Clinical Trials /

Abatacept, Ixazomib Citrate, and Dexamethasone in Treating Patients With Multiple Myeloma Resistant to Chemotherapy

NCT03457142

Description:

This phase II trial studies how well abatacept, ixazomib citrate, and dexamethasone work in treating patients with multiple myeloma that is resistant to chemotherapy. Abatacept may block certain proteins that are present on multiple myeloma cells that have been shown to protect against chemotherapy. Drugs used in chemotherapy, such as ixazomib citrate and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving abatacept, ixazomib citrate, and dexamethasone may work better at treating patients with multiple myeloma resistant to chemotherapy.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abatacept, Ixazomib Citrate, and Dexamethasone in Treating Patients With Multiple Myeloma Resistant to Chemotherapy
  • Official Title: Phase II Study of Targeting CD28 in Multiple Myeloma With Abatacept (CTLA4-Ig) to Overcome Resistance to Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: I 47217
  • SECONDARY ID: NCI-2017-02430
  • SECONDARY ID: I 47217
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03457142

Conditions

  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma

Interventions

DrugSynonymsArms
AbataceptBMS-188667, CTL A4-Ig B7 Inhibitor, CTLA4-Ig, cytotoxic T lymphocyte-associated antigen-4, Orencia, RG2077Treatment (abatacept, ixazomib citrate, dexamethasone)
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 (abatacept, ixazomib citrate, dexamethasone)
Ixazomib CitrateMLN-9708, MLN9708, NinlaroTreatment (abatacept, ixazomib citrate, dexamethasone)

Purpose

This phase II trial studies how well abatacept, ixazomib citrate, and dexamethasone work in treating patients with multiple myeloma that is resistant to chemotherapy. Abatacept may block certain proteins that are present on multiple myeloma cells that have been shown to protect against chemotherapy. Drugs used in chemotherapy, such as ixazomib citrate and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving abatacept, ixazomib citrate, and dexamethasone may work better at treating patients with multiple myeloma resistant to chemotherapy.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the therapeutic efficacy (as measured by response rate) of abatacept +
      ixazomib citrate (ixazomib) + dexamethasone in multiple myeloma patients who have relapsed
      (or who are primary refractory) following treatment with their first proteasome
      inhibitor-containing regimen (excluding ixazomib), compared to historical controls of
      ixazomib + dexamethasone.

      SECONDARY OBJECTIVES:

      I. To assess the toxicity profile of abatacept + ixazomib + dexamethasone in multiple myeloma
      patients who have relapsed (or who are primary refractory) following treatment with their
      first proteasome inhibitor-containing regimen, compared to historical controls of ixazomib +
      dexamethasone.

      II. To assess progression-free and overall survival profile of abatacept + ixazomib +
      dexamethasone in multiple myeloma patients who have relapsed (or who are primary refractory)
      following treatment with their proteasome inhibitor-containing regimen, compared to
      historical controls of ixazomib + dexamethasone.

      TERTIARY OBJECTIVES:

      I. Assess whether myeloma expression of CD28, CD86, serum kynurenine and/or IL-6 are
      correlated with specific clinical outcomes.

      OUTLINE:

      Patients receive abatacept intravenously (IV) over 30 minutes on day 1 of course 1, then
      subcutaneously (SC) on days 2, 8, 15, and 22 of course 1, and then on days 1, 8, 15, and 22
      of subsequent courses. Patients also receive ixazomib citrate orally (PO) once daily (QD) on
      days 1, 8, and 15 and dexamethasone on days 1, 8, 15, and 22. Courses repeat every 28 days in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abatacept, ixazomib citrate, dexamethasone)ExperimentalPatients receive abatacept IV over 30 minutes on day 1 of course 1, then SC on days 2, 8, 15, and 22 of course 1, and then on days 1, 8, 15, and 22 of subsequent courses. Patients also receive ixazomib citrate PO QD on days 1, 8, and 15 and dexamethasone on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Abatacept
  • Dexamethasone
  • Ixazomib Citrate

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with multiple myeloma who have relapsed (or who are primary refractory)
             following treatment with a proteasome inhibitor-containing regimen (excluding
             ixazomib) and who have not been treated with a second proteasome inhibitor (ixazomib,
             bortezomib, carfilzomib or other proteasome inhibitor).

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study
             entry

          -  Must be free of systemic infection:

               -  Subjects with active infections (whether or not they require antibiotic therapy)
                  may be eligible after complete resolution of the infection

               -  Subjects on antibiotic therapy must be off antibiotics for at least 7 days before
                  beginning treatment

          -  Absolute neutrophil count >= 750/mm^3

          -  Platelet count >= 25,000/mm^3

          -  Creatinine clearance >= 30 mL/min

          -  Total bilirubin =< 3 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
             ULN

          -  Patient's multiple myeloma cells are positive for CD28 or CD86 expression by flow
             cytometry or immunohistochemistry (in any proportion) CD28 or CD86 positivity can have
             been determined on previous bone marrow aspirates or biopsies

          -  Disease free of prior malignancies for > 2 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma ?in situ? of the cervix
             or breast

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry; should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately

          -  Participant or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent form prior to receiving any study related procedure

        Exclusion Criteria:

          -  Prior treatment with ixazomib

          -  Inability to take ixazomib or abatacept

          -  Life expectancy less than 4 months

          -  Patients with a known diagnosis of plasma cell leukemia

          -  Known active tuberculosis or fungal infection

          -  Known seropositive for or active viral infection with, human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)

          -  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

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or, which
             confounds the ability to interpret data from the study

          -  Pregnant or nursing female participants

          -  Unwilling or unable to follow protocol requirements

          -  Any condition which in the investigator?s opinion deems the participant an unsuitable
             candidate to receive study drug

          -  Received an investigational agent within 30 days prior to enrollment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate of abatacept + ixazomib citrate + dexamethasone in multiple myeloma patients
Time Frame:Up to 1.5 years
Safety Issue:
Description:Will be compared to historical controls of ixazomib citrate + dexamethasone. Responses to treatment will be measured by serum immunoglobulins, serum free kappa and lambda light chains, serum protein electrophoresis/immunofixation electrophoresis, and 24-hour urine protein electrophoresis/immunofixation. International uniform response criteria will be used. The anti-myeloma activity will be evaluated on an exploratory basis and will be summarized using descriptive statistics or graphical methods. No formal comparison will be carried forth.

Secondary Outcome Measures

Measure:Incidence of adverse events assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 30 days after last dose
Safety Issue:
Description:The adverse events and drug related toxicities will be summarized by grade using frequencies and relative frequencies. The rate of grade 3 or higher toxicities that are probably or definitely related to abatacept will be reported with 90% confidence intervals obtained using Jeffrey?s prior method.
Measure:Overall survival
Time Frame:From the date of the first study treatment until initiation of a new therapy or until death, whichever occurs first, assessed up to 1.5 years
Safety Issue:
Description:Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.
Measure:Progression-free survival
Time Frame:From the date of the first study treatment to the date of first observed disease progression or death due to any cause, assessed up to 1.5 years
Safety Issue:
Description:Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated

December 3, 2019