Recurrent Plasma Cell MyelomaPhase 2NCT03457142
Abatacept, Ixazomib Citrate, and Dexamethasone in Treating Patients With Multiple Myeloma Resistant to Chemotherapy
A Phase 2 study testing Abatacept, Dexamethasone and Ixazomib Citrate in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Roswell Park Cancer Institute at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Abatacept, Dexamethasone and Ixazomib Citrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesUnited States
- Study dates
- 11 Sep 2018to 6 Nov 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
St. Francis Hospital
East Hills, New York, 11548
Good Samaritan Hospital
West Islip, New York, 11795
About this study
Official title: Phase II Study of Targeting CD28 in Multiple Myeloma With Abatacept (CTLA4-Ig) to Overcome Resistance to Chemotherapy
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:
- 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:
- 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:
- 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.
- Being tested
- Abatacept, Dexamethasone, Ixazomib Citrate, Laboratory Biomarker Analysis
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptBiological
Also called BMS-188667, CTL A4-Ig B7 Inhibitor, CTLA4-Ig, cytotoxic T lymphocyte-associated antigen-4
Given IV and SC
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
Ixazomib CitrateDrug
Also called MLN-9708, MLN9708, Ninlaro
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (abatacept, ixazomib citrate, dexamethasone) | Experimental | 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. Receives: Biological: Abatacept; Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 cycle of 28 days
Secondary outcomes (3)
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.
Measured: Up to 30 days after last dose
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.
Measured: 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.
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start11 Sep 2018
- Primary completion21 Nov 2022
- Study completion6 Nov 2024
Why it stopped: funding ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Jens Hillengass, MD, PhD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03457142
- Sponsor's protocol ID
- I 47217
- Other IDs
- NCI-2017-02430, I 47217
- Status last verified
- Feb 2025
- First submitted
- 27 Feb 2018
- Last updated
- 4 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Targeting CD28 in Multiple Myeloma With Abatacept (CTLA4-Ig) to Overcome Resistance to Chemotherapy
- ClinicalTrials.gov ID
- NCT03457142
- Acronym / sponsor ID
- I 47217
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: funding ended
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 11 Sep 2018 (actual)
- Primary completion
- 21 Nov 2022 (actual)
- Study completion
- 6 Nov 2024 (actual)
- First posted
- 7 Mar 2018 (actual)
- Results
- Posted 16 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (abatacept, ixazomib citrate, dexamethasone) | Experimental | Biological: Abatacept, Drug: Dexamethasone, Drug: Ixazomib Citrate, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
- Absolute neutrophil count >= 750/mm^3
- Platelet count >= 25,000/mm^3
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbataceptAlso: BMS-188667, CTL A4-Ig B7 Inhibitor, CTLA4-Ig, cytotoxic T lymphocyte-associated antigen-4Given IV and SC | Biological | Treatment (abatacept, ixazomib citrate, dexamethasone) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO | Drug | Treatment (abatacept, ixazomib citrate, dexamethasone) |
| Ixazomib CitrateAlso: MLN-9708, MLN9708, NinlaroGiven PO | Drug | Treatment (abatacept, ixazomib citrate, dexamethasone) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (abatacept, ixazomib citrate, dexamethasone) |
Primary outcome
Response Rate of Abatacept + Ixazomib Citrate + Dexamethasone in Multiple Myeloma Patients
Time frame: 1 cycle of 28 days
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.
3 secondary outcomes
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
Overall Survival
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.
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 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Hillengass, MD, PhD principal investigator
Roswell Park Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abatacept, Dexamethasone and Ixazomib Citrate in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Roswell Park Cancer Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate of Abatacept + Ixazomib Citrate + Dexamethasone in Multiple Myeloma Patients (time frame: 1 cycle of 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.