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TerminatedNCT03457142Updated Mar 4, 2025Results posted

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

A Phase 2 interventional study of Abatacept and Dexamethasone in Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, sponsored by Roswell Park Cancer Institute. Terminated at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-04.

Sponsored by Roswell Park Cancer Institute · Phase 2, Interventional, and Treatment

Why this study was terminated
funding ended
Phase
Phase 2
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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 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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • Experimental
    Treatment (abatacept, ixazomib citrate, dexamethasone)

    Patients 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.

    Biological: Abatacept · Drug: Dexamethasone · Drug: Ixazomib Citrate · Other: Laboratory Biomarker Analysis

Interventions

  • BiologicalAbatacept

    Given IV and SC

    Also known as: BMS-188667, CTL A4-Ig B7 Inhibitor, CTLA4-Ig, cytotoxic T lymphocyte-associated antigen-4, Orencia, RG2077

  • DrugDexamethasone

    Given PO

    Also known as: Aacidexam, 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, Visumetazone

  • DrugIxazomib Citrate

    Given PO

    Also known as: MLN-9708, MLN9708, Ninlaro

  • OtherLaboratory Biomarker Analysis

    Correlative studies

05

What researchers measure

Primary outcomes

  1. Response Rate of Abatacept + Ixazomib Citrate + Dexamethasone in Multiple Myeloma Patients

    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.

    Time frame: 1 cycle of 28 days

Secondary outcomes

  1. Incidence of Adverse Events Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

    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.

    Time frame: Up to 30 days after last dose

  2. Overall Survival

    Defined as the time from treatment initiation until death or last follow-up. Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.

    Time frame: From the date of the first study treatment until initiation of a new therapy, death, or end of follow-up (up to 5 years); whichever occurs first.

  3. Progression-free Survival

    Defined as the time from treatment initiation until disease progression, death, or last follow-up. Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.

    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 5 years

Other outcomes

  1. CD28 and CD86 Expression Assessed by Flow Cytometry

    The expression/levels and response will be evaluated using logistic regression models.

    Time frame: Up to 5 years

  2. Serum Kynurenine and IL-6 Levels

    The association between CD28, CD86, serum kynurenine and IL-6 expression/levels and response will be evaluated using logistic regression models.

    Time frame: Up to 5 years

06

Results

Posted May 16, 2024

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Started15
Completed14
Not completed1
Withdrew: Death1

Outcome measures

PrimaryResponse Rate of Abatacept + Ixazomib Citrate + Dexamethasone in Multiple Myeloma Patients

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.

Time frame:
1 cycle of 28 days
Reported as:
Count of participants · Participants
Response Rate of Abatacept + Ixazomib Citrate + Dexamethasone in Multiple Myeloma Patients
ParticipantsTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Complete Response1
Partial Response4
Stable Disease8
Progressive Disease1
SecondaryIncidence of Adverse Events Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

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.

Time frame:
Up to 30 days after last dose
Reported as:
Count of participants · Participants
Incidence of Adverse Events Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
ParticipantsTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Incidence of Adverse Events Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.05
Statistical analysis
  • Treatment (Abatacept, Ixazomib Citrate, Dexamethasone) · Grade 3+ treatment related ae rate: 0.33 · 90% CI 0.17 to 0.54
SecondaryOverall Survival

Defined as the time from treatment initiation until death or last follow-up. Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.

Time frame:
From the date of the first study treatment until initiation of a new therapy, death, or end of follow-up (up to 5 years); whichever occurs first.
Reported as:
Median · months
Overall Survival
monthsTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Overall Survival33.6 (14.5 to NA)
SecondaryProgression-free Survival

Defined as the time from treatment initiation until disease progression, death, or last follow-up. Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.

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 5 years
Reported as:
Median · months
Progression-free Survival
monthsTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Progression-free Survival11.1 (5.7 to 15.9)
Other pre-specifiedCD28 and CD86 Expression Assessed by Flow Cytometry

The expression/levels and response will be evaluated using logistic regression models.

Time frame:
Up to 5 years

No measurements were reported for this outcome.

Other pre-specifiedSerum Kynurenine and IL-6 Levels

The association between CD28, CD86, serum kynurenine and IL-6 expression/levels and response will be evaluated using logistic regression models.

Time frame:
Up to 5 years

No measurements were reported for this outcome.

Adverse events

Collected over Adverse events were captured from the start of treatment until up to 30 days after the end of treatment; which ranged from 1.4 to 16.6 months (median = 6.8 months). All-cause mortality is captured for up to 5 years post treatment initiation.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Abatacept, Ixazomib Citrate, Dexamethasone)1/15 (6.7%)1/15 (6.7%)14/15 (93.3%)
Most frequent serious events
Most frequent serious events
EventTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
DiarrheaGastrointestinal disorders1/15
Platelet count decreasedInvestigations1/15
Most frequent other events
Showing 10 of 37
Most frequent other events
EventTreatment (Abatacept, Ixazomib Citrate, Dexamethasone)
DiarrheaGastrointestinal disorders8/15
FatigueGeneral disorders6/15
InsomniaPsychiatric disorders6/15
Platelet count decreasedInvestigations3/15
Sinus tachycardiaCardiac disorders2/15
Blurred visionEye disorders2/15
Gastroesophageal reflux diseaseGastrointestinal disorders2/15
Edema limbsGeneral disorders2/15
Generalized edemaGeneral disorders2/15
DizzinessNervous system disorders2/15

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Mean64.2 ± 10.2
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Abatacept, Ixazomib Citrate, Dexamethasone)
Female5
Male10
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Abatacept, Ixazomib Citrate, Dexamethasone)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White15
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Treatment (Abatacept, Ixazomib Citrate, Dexamethasone)
United States15
07

Study locations

3 sites
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • St. Francis Hospital
    East Hills, New York 11548, United States
  • Good Samaritan Hospital
    West Islip, New York 11795, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jul 29, 2021

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03457142
Lead sponsor
Roswell Park Cancer Institute
Collaborators
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Mar 7, 2018
Start date
Sep 11, 2018
Primary completion
Nov 21, 2022
Completion
Nov 6, 2024
Results posted
May 16, 2024
Last update
Mar 4, 2025

Study contacts

Jens Hillengass, MD, PhD
principal investigator · Roswell Park Cancer Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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