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

NCT03457142 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: I 47217NCI-2017-02430
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

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.

  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

  Up to 30 days after last dose

• Overall Survival

  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

  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 (2)

• CD28 and CD86 Expression Assessed by Flow Cytometry

  Up to 5 years

• Serum Kynurenine and IL-6 Levels

  Up to 5 years

Study Arms (1)

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.

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

Interventions

Abatacept BIOLOGICAL

Given IV and SC

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

Treatment (abatacept, ixazomib citrate, dexamethasone)

Dexamethasone DRUG

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

Treatment (abatacept, ixazomib citrate, dexamethasone)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (abatacept, ixazomib citrate, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (abatacept, ixazomib citrate, dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

St. Francis Hospital

East Hills, New York, 11548, United States

Location

Good Samaritan Hospital

West Islip, New York, 11795, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Abatacept; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ixazomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Kris Attwood
• Organization: Roswell Park Comprehensive Cancer Center

Kris.Attwood@roswellpark.org

716-845-2300

Study Officials

• Jens Hillengass, MD, PhD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2018
• First Posted: March 7, 2018
• Study Start: September 11, 2018
• Primary Completion: November 21, 2022
• Study Completion: November 6, 2024
• Last Updated: March 4, 2025
• Results First Posted: May 16, 2024

Record last verified: 2025-02

Locations

US (3)