Multiple Myeloma Clinical Trial

Isatuximab, Carfilzomib, and Pomalidomide for the Treatment of Relapsed or Refractory Multiple Myeloma

Summary

This phase II trial studies the effect of treatment-a-promising-new-option-for-relapsed-multiple-myeloma/" >isatuximab, carfilzomib, and pomalidomide in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Isatuximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab, carfilzomib, and pomalidomide may help treat patients with multiple myeloma.

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Full Description

PRIMARY OBJECTIVE:

I. To assess the rate of response following treatment with isatuximab combined with carfilzomib and pomalidomide (isatuximab [Isa] carfilzomib [Car] pomalidomide [Pom]).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of the IsaCarPom combination. II. To assess duration of disease response following treatment with the IsaCarPom regimen.

III. To assess depth of IsaCarPom treatment as it relates to timing of subsequent therapies.

IV. To assess progression-free survival associated with IsaCarPom. V. To assess overall survival associated with IsaCarPom.

EXPLORATORY OBJECTIVE:

I. To molecularly assess the depth of IsaCarPom treatment by measuring minimal residual disease (MRD).

OUTLINE:

Patients receive isatuximab intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of subsequent cycles, carfilzomib IV over 10 to 30 minutes on days 1, 8, 15, and pomalidomide orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 24 months.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Participant or legally authorized representative (LAR) must provide written informed consent before any study specific procedures or interventions are performed
Participants must be >= 18 years of age
Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined by 2016 International Myeloma Working Group (IMWG) criteria

Relapsed or refractory multiple myeloma, defined as meeting one or more of the following:

Nonresponsive to most recent therapy (stable disease or progressive disease [PD] while on treatment), or
Disease progression within 60 days of discontinuation from most recent therapy

Participant has received at least 1 line of prior therapy.

Prior exposure to proteasome inhibitor is permitted, with a 2 week washout period from last dose
Prior exposure to immunomodulatory imide drug (IMiD) therapy (lenalidomide, pomalidomide, or thalidomide) is permitted, with a 2 week washout period from last dose
Prior treatment with anti-CD38 therapy (e.g., daratumumab) is permitted, following a 6 month washout period from last dose

Measurable disease with at least one of the following:

Monoclonal immunoglobulin spike on serum protein electrophoresis of >= 0.5 g/dL
Urine monoclonal immunoglobulin spike of >= 200 mg/24 hours
Involved free light chain (FLC) >= 10 mg/dL and an abnormal serum FLC ratio (i.e., < 0.26 or > 1.65)
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
Toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with anti-CD38 therapy should be resolved to baseline or less than grade 1
Anticipated life expectancy of at least 6 months (per investigator discretion)
No contraindication to receiving thromboprophylaxis for pomalidomide

Patients must have normal marrow and organ function as defined by:

Absolute neutrophil count >= 1,000/uL
Platelets >= 75,000/uL
Hemoglobin concentration of >= 8.0 g/dL within 14 days prior to registration. Patients may have received transfusion if greater than 7 days prior to registration

Must have adequate liver function, as defined by:

Total bilirubin =< 2 x institutional upper limits of normal (IULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 x IULN

Must have adequate renal function, as defined by:

Creatinine clearance (CrCl) of >= 30 mL/min, as measured by a 24-hour urine collection or as estimated by the Cockcroft and Gault formula. The serum creatinine value used in the calculation must have been obtained within 35 days prior to registration.
For patients with a creatinine clearance within the range of 30-45 mL/min, stability (i.e., not deteriorating) must be demonstrated over a period of 8 weeks prior to enrollment in the study
Left ventricular ejection fraction (LVEF) by echocardiogram >= 40% within 35 days prior to initiating study treatment
Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to receiving the first dose of study medication. If the urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female participants of childbearing potential (FOCBP) must agree to use highly-effective method(s) of contraception during the study and for 3 months after the last dose of study drug. FOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year without an alternative medical cause
Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study drug

Exclusion Criteria:

Waldenstrom macroglobulinemia
Multiple myeloma of immunoglobulin M (IgM) subtype
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard differential)
Myelodysplastic syndrome
Participants with known or suspected amyloidosis
Individuals that are refractory to prior treatment with either carfilzomib or pomalidomide
Intolerance leading to discontinuation of either carfilzomib or pomalidomide
Prior allogeneic stem cell transplant
Second malignancy requiring concurrent treatment or those with non-hematological malignancies (except non-melanoma skin cancers). Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the principal investigator (PI). Cancer treated with curative intent > 5 years previously is allowed
Any known allergies or hypersensitivity to isatuximab or other monoclonal antibody therapies and required premedications
Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
Hypersensitivity to any of the components of study therapy that is not amenable to premedication with steroids and H2 blockers

Participant has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, of the first dose of study medication. Wash-out period of prior anti-CD38 therapy (e.g. Daratumumab) is 6 months before first dose of study medication.

Exception: Emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg per day for a maximum of 4 days) before treatment is not a barrier to eligibility
Participant has undergone autologous stem cell transplant within 90 days of the first dose of study medication

Ongoing adverse events related to a previously administered anti-myeloma therapy (including radiation therapy) >= grade 1

Exception: Potential participants with =< grade 2 neuropathy may, at the discretion of the investigator, qualify for the study
Active autoimmune disease, except vitiligo or hypothyroidism
Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, chronic obstructive pulmonary disease [COPD], allergic rhinitis, or dermatologic conditions) and the emergency use of corticosteroids outlined above
Known human immunodeficiency virus (HIV) infection
Ongoing or active systemic infection
Seropositive for hepatitis B virus (HBV) defined by a positive test for hepatitis B surface antigen (HBsAg). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. Exception: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
Seropositive for hepatitis C virus (HCV) (except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy)
Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV), pulmonary hypertension, unstable angina, or myocardial infarction within the past 6 months
Participant has received a live vaccine within 30 days of planned start of study therapy
A history of non-infectious pneumonitis that required treatment with steroids, or current pneumonitis
Diagnosis of immunodeficiency or treatment with any form of immunosuppressive therapy within 7 days prior to the first dose of study medication
Pregnant or breastfeeding
Any medical or psychiatric conditions that in the opinion of the PI would preclude safe participation in protocol

Study is for people with:

Multiple Myeloma

Phase:

Phase 2

Estimated Enrollment:

44

Study ID:

NCT04850599

Recruitment Status:

Recruiting

Sponsor:

OHSU Knight Cancer Institute

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There is 1 Location for this study

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OHSU Knight Cancer Institute
Portland Oregon, 97239, United States More Info
Rebecca W. Silbermann
Contact
503-494-5304
[email protected]
Rebecca W. Silbermann
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 2

Estimated Enrollment:

44

Study ID:

NCT04850599

Recruitment Status:

Recruiting

Sponsor:


OHSU Knight Cancer Institute

How clear is this clinincal trial information?

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