Abatacept, Ixazomib Citrate, and Dexamethasone in Treating Patients With Multiple Myeloma Resistant to Chemotherapy
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| ClinicalTrials.gov Identifier: NCT03457142 |
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Recruitment Status :
Recruiting
First Posted : March 7, 2018
Last Update Posted : May 9, 2019
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Sponsor:
Roswell Park Cancer Institute
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma | Biological: Abatacept Drug: Dexamethasone Drug: Ixazomib Citrate Other: Laboratory Biomarker Analysis | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 19 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Study of Targeting CD28 in Multiple Myeloma With Abatacept (CTLA4-Ig) to Overcome Resistance to Chemotherapy |
| Actual Study Start Date : | June 25, 2018 |
| Estimated Primary Completion Date : | November 8, 2019 |
| Estimated Study Completion Date : | November 8, 2020 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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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.
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Biological: Abatacept
Given IV and SC
Other Names:
Drug: Dexamethasone Given PO
Other Names:
Drug: Ixazomib Citrate Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies |
Primary Outcome Measures :
- Response rate of abatacept + ixazomib citrate + dexamethasone in multiple myeloma patients [ Time Frame: Up to 1.5 years ]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 :
- 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 ]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.
- 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 ]Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.
- 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 ]Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and survival rates will be obtained with 90% confidence intervals.
Other Outcome Measures:
- CD28 and CD86 expression assessed by flow cytometry [ Time Frame: Up to 1.5 years ]The expression/levels and response will be evaluated using logistic regression models.
- Serum kynurenine and IL-6 levels [ Time Frame: Up to 1.5 years ]The association between CD28, CD86, serum kynurenine and IL-6 expression/levels and response will be evaluated using logistic regression models.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03457142
Locations
| United States, New York | |
| Roswell Park Cancer Institute | Recruiting |
| Buffalo, New York, United States, 14263 | |
| Contact: Kelvin P. Lee 716-845-4106 Kelvin.Lee@roswellpark.org | |
| Principal Investigator: Kelvin P. Lee | |
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Kelvin Lee | Roswell Park Cancer Institute |
| Responsible Party: | Roswell Park Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT03457142 History of Changes |
| Other Study ID Numbers: |
I 47217 NCI-2017-02430 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) I 47217 ( Other Identifier: Roswell Park Cancer Institute ) P30CA016056 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 7, 2018 Key Record Dates |
| Last Update Posted: | May 9, 2019 |
| Last Verified: | May 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
| Product Manufactured in and Exported from the U.S.: | Yes | |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Dexamethasone acetate Ixazomib BB 1101 Citric Acid Sodium Citrate Abatacept Glycine Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones |