Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma

NCT03756896 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: IRB00097882NCI-2017-02052Winship4101-17P30CA138292
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well carfilzomib, pomalidomide, and dexamethasone work in treating patients with high-risk multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, 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 carfilzomib, pomalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Conditions

Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• ≥ Complete response (CR) rates

  Completed response (CR) rates will be determined for CPd maintenance.

  Up to 2 years after study start

Secondary Outcomes (6)

• Progression-free survival (PFS)

  From first dose until documented progression or death, assessed at 18 months

• Best response on-study

  Up to 2 years after study start

• Objective response rate (ORR) defined as the proportion of treated subjects who achieve a best response of CR, stringent complete response (sCR), very good partial response (VGPR), or partial response (PR)

  Up to 2 years after study start

• Duration of response (DOR)

  From first response (PR or better) until a progression event (documented progression or death), assessed up to 2 years

• Overall survival (OS)

  Up to 2 years after study start

Study Arms (1)

Carfilzomib, pomalidomide, dexamethasone

EXPERIMENTAL

Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide PO daily on days 1-21, and dexamethasone PO daily on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Pomalidomide

Interventions

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Carfilzomib, pomalidomide, dexamethasone

Dexamethasone DRUG

Given PO

Also known as: Decadron, Dekacort, Dexameth, Hexadrol

Carfilzomib, pomalidomide, dexamethasone

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst

Carfilzomib, pomalidomide, dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patients must meet the following criteria on screening examination to be eligible to participate in the study; all laboratory assessments should be performed within 28 days of initiation of protocol therapy unless otherwise specified; subject is, in the investigator's opinion, willing and able to comply with the protocol requirements
• Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
• Subject is a transplant-eligible patient that have undergone autologous stem cell transplant (ASCT) within one year of their diagnosis and have achieved ≥ partial response (PR) based on International Myeloma Working Group (IMWG) standard criteria
• Patients with high risk disease defined as
• Presence of del(17p); t(4;14); t(14;16); t(14;20) by fluorescence in situ hybridization (FISH) or by cytogenetics (CTG)
• Plasma cell leukemia at diagnosis with ≥ 20% circulating plasma cells on peripheral blood
• Subject agrees to refrain from blood donations during therapy on study and for 90 days after therapy is completed
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International units (mIU)/mL within 10-14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide through 90 days after the last dose of study drug; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug; all patients must be registered in and must comply with all requirements of the pomalidomide Risk Evaluation and Mitigation Strategies (REMS) program; male subjects should refrain from sperm donation for at least 90 days after the last dose of carfilzomib or pomalidomide
• FCBP refers to sexually mature female, regardless of sexual orientation or whether they have undergone tubal ligation, who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally menopausal for at least 24 consecutive months

You may not qualify if:

• Diagnosed with smoldering multiple myeloma (MM), monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis or standard risk myeloma or secondary plasma cell leukemia
• High risk patients that did not achieve ≥ PR after stem cell transplant
• Participant has ≥ grade 2 peripheral neuropathy on clinical examination within 21 days before initiation of protocol therapy
• Creatinine clearance \< 30 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy; the Cockcroft-Gault formula should be used for calculating creatinine clearance values
• Platelet count \< 75,000 cells/mm³ at time of screening evaluation; transfusion may not be used to meet platelet eligibility criteria within 7 days of obtaining screening evaluation
• Participants with an absolute neutrophil count (ANC) \< 1000 cells/mm³ at time of screening evaluation; growth factors may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation
• Participants with hemoglobin level \< 8.0 g/dL, at time of screening; transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation
• Bilirubin \> 1.5 x institutional upper limit of normal (ULN), within 21 days of initiation of protocol therapy
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]), or alkaline phosphatase \> 3 x institutional ULN, within 21 days of initiation of protocol therapy
• Other ongoing or prior anti-myeloma therapy; patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. once daily \[q.d.\] or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment)
• Known significant cardiac abnormalities including:
• Congestive heart failure, New York Heart Association (NYHA) class III or IV
• Uncontrolled angina, arrhythmia or hypertension
• Myocardial infarction within the past six months
• Any other uncontrolled or severe cardiovascular condition

Sponsors & Collaborators

• Emory University: lead
• Amgen: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate; pomalidomide

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)

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

Study Officials

• Ajay Nooka, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Study Start: January 25, 2019
• Primary Completion: June 24, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 30, 2025

Record last verified: 2025-04

Locations

US (1)