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

Recurrent Plasma Cell Myeloma Clinical Trial

Official title:

Phase II Study of Targeting CD28 in Multiple Myeloma With Abatacept (CTLA4-Ig) to Overcome Resistance to Chemotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03457142
• Other study ID #: I 47217
• Secondary ID: NCI-2017-02430I
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 11, 2018
• Est. completion date: January 11, 2025

Study information

• Verified date: May 2024
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: January 11, 2025
• Est. primary completion date: November 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Intervention

Biological:
• Abatacept
Given IV and SC

Drug:
• Dexamethasone
Given PO
• Ixazomib Citrate
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	St. Francis Hospital	East Hills	New York
United States	Good Samaritan Hospital	West Islip	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CD28 and CD86 Expression Assessed by Flow Cytometry	The expression/levels and response will be evaluated using logistic regression models.	Up to 5 years
Other	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.	Up to 5 years
Primary	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.	1 cycle of 28 days
Secondary	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.	Up to 30 days after last dose
Secondary	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.	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.
Secondary	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.	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