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

Study Purpose

This phase II trial studies the effect of isatuximab, carfilzomib, pomalidomide, and dexamethasone 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 proteins needed for cell growth. Pomalidomide may help shrink or slow the growth of mutliple myeloma. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving isatuximab, carfilzomib, pomalidomide, and dexamethasone may kill more cancer cells.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients with relapsed or refractory multiple myeloma, with >= 1 prior therapy.
  • - Must have received prior lenalidomide therapy.
  • - Must have measurable disease, as defined by International Myeloma Working Group criteria, having one or more of the following: - Serum M protein >= 0.5 g/dL.
  • - Urine M protein >= 200 mg/24 hours.
  • - Involved serum free light chain level >= 10 mg/dL with abnormal kappa/lambda ratio.
  • - Measurable biopsy-proven plasmacytomas (>= 1 lesion has a single diameter >= 2 cm) - Bone marrow plasma cells >= 30% - Age 18 years and older, and have the capacity to give informed consent.
  • - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • - Subjects should have resolution of any toxicities from prior therapy to grade =< 1 or baseline prior to enrollment (with the exception of peripheral neuropathy) - Subjects are required to have grade =< 2 peripheral neuropathy to enroll.
  • - Prior autologous stem cell transplant is allowed; patients must be >= 6 months post- autologous stem cell transplantation to enroll.
  • - Estimated glomerular filtration rate (eGFR) >= 20 ml/min.
  • - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) - Total bilirubin =< 2 x ULN.
  • - Absolute neutrophil count (ANC) >= 1,000/uL.
  • - Platelets >= 50,000/uL.
  • - Hemoglobin >= 8 g/dL.
  • - Growth factor use or transfusions may be used to meet the eligibility requirement for ANC, platelets, and hemoglobin.
  • - Female patients of childbearing potential and male patients must agree to use 2 effective forms of contraception or continuously abstain from heterosexual intercourse during the period of therapy, and for 6 months after discontinuation of study treatment for females and 3 months after discontinuation of study treatment for males.

Exclusion Criteria:

  • - History of clinically significant cardiovascular disease, including congestive heart failure New York Heart Association (NYHA) class 3-4, symptomatic ischemia, left ventricular ejection fraction < 40%, uncontrolled conduction abnormalities, myocardial infarction in last 6 months.
  • - Uncontrolled hypertension as determined by the principal investigator (PI) or designee.
  • - Active plasma cell leukemia or systemic amyloid light-chain (AL) amyloidosis.
  • - History of another primary malignancy that has not been in remission for at least 1 year (with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated superficial bladder cancer and cervical carcinoma in site on biopsy or a squamous intraepithelial lesion on papanicolaou [PAP] smear) - For patients with chronic hepatitis B viral infection, the hepatitis B virus (HBV) polymerase chain reaction (PCR) must be undetectable on suppressive therapy.
  • - Patients with a history of Hepatitis C viral infection must have been treated and cured.
For patients on treatment for hepatitis C, they are eligible if they have an undetectable hepatitis C virus (HCV) viral load.
  • - Subjects with active uncontrolled infection.
  • - Concurrent use of other anticancer agents or experimental treatments.
- Treatment with anti-CD38 monoclonal antibody therapy in the last 90 days

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04883242
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Washington
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Andrew J. Cowan
Principal Investigator Affiliation Fred Hutch/University of Washington Cancer Consortium
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Recurrent Multiple Myeloma, Refractory Multiple Myeloma
Additional Details

OUTLINE: INDUCTION: Patients receive isatuximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide orally (PO) once daily (QD) on days 1-21, and dexamethasone PO or IV on days 1,8, 15, and 22. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive isatuximab IV days 1 and 15, carfilzomib IV over 30 minutes on days 1 and 15, pomalidomide PO QD on days 1-21, and dexamethasone PO or IV on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then for up to 5 years.

Arms & Interventions

Arms

Experimental: Treatment (isatuximab, carfilzomib, pomalidomide, steroid)

INDUCTION: Patients receive isatuximab IV on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide PO QD on days 1-21, and dexamethasone PO or IV on days 1,8, 15, and 22. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive isatuximab IV days 1 and 15, carfilzomib IV over 30 minutes on days 1 and 15, pomalidomide PO QD on days 1-21, and dexamethasone PO or IV on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - Carfilzomib

Given IV

Drug: - Dexamethasone

Given PO or IV

Biological: - Isatuximab

Given IV

Drug: - Pomalidomide

Given PO

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Seattle, Washington

Status

Recruiting

Address

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

Site Contact

Andrew J. Cowan

ajcowan@seattlecca.org

206-667-4551