Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT01665794 | Completed Phase 1 FDA Drug

• 2 other identifiers: 12-1088NCI-2012-01168
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 5

Brief Summary

The study will investigate the effects of adding carfilzomib to the combination of pomalidomide and dexamethasone in sequential dose escalation cohorts in patients with relapsed or refractory multiple myeloma. This portion of the study is complete. This study will also investigate the effects of adding daratumumab to the combination of carfilzomib, pomalidomide and dexamethasone.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of carfilzomib when administered in combination with pomalidomide and dexamethasone

  28 days

• Partial response rate after 4 courses according to International Myeloma Working Group (IMWG) criteria

  The proportion and exact 95% binomial confidence interval for the response rate will be reported adjusted for the two-stage design of this trial.

  4 months

• Response rates of carfilzomib, pomalidomide, dexamethasone, and daratumumab dosing according to International Myeloma Working Group (IMWG) criteria

  4 months

Secondary Outcomes (5)

• Overall response rate

  Up to 2 years

• Time to progression

  Up to 2 years

• Duration of response

  From the date of the clinical examination which confirmed the response, until the date of disease progression, or censoring at the date of last clinical follow-up up to 2 years

• Progression-free survival

  From the date of first therapy until the date of documented disease progression or death up to 2 years

• Overall survival

  Up to 2 years

Study Arms (2)

PdC Group

EXPERIMENTAL

Patients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.

Drug: Pomalidomide; Drug: Carfilzomib; Drug: dexamethasone

PdC + Dara Group

EXPERIMENTAL

Patients receive carfilzomib, pomalidomide, dexamethasone, and daratumumab at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.

Drug: Pomalidomide; Drug: Carfilzomib; Drug: dexamethasone; Drug: Daratumumab

Interventions

Carfilzomib DRUG

Carfilzomib given by intravenous (IV) infusion at assigned dose.

Also known as: Kyprolis (R), PR-171

PdC + Dara Group; PdC Group

dexamethasone DRUG

Dexamethasone taken orally of given by IV infusion.

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

PdC + Dara Group; PdC Group

Daratumumab DRUG

Daratumumab given by intravenous (IV) infusion at assigned dose.

Also known as: Daralex

PdC + Dara Group

Pomalidomide DRUG

Pomalidomide taken orally at assigned dose.

Also known as: CC-4047, Pomalyst(R)

PdC + Dara Group; PdC Group

Eligibility Criteria

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

You may qualify if:

• Relapsed and relapsed/refractory multiple myeloma requiring systemic therapy
• Failed at least one prior treatment for multiple myeloma (must have received lenalidomide)
• To be enrolled as second line therapy: Must be refractory to lenalidomide (progression on therapy or within 60 days of lenalidomide dosing)
• Measurable disease, as indicated by one or more of the following:
• Serum M-protein \>= 0.5 g/dL
• Urine M-protein \>= 200 mg/24 hours
• If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
• Involved serum free light chains ≥ 10 mg/dL (free light change ratio must be abnormal)
• Aged 18 years or older
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate Liver Function
• Bilirubin \< 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) \< 2.5 times ULN
• Alanine aminotransferase (ALT) \< 2.5 times ULN

You may not qualify if:

• Patients for whom there is the prospect of stem cell transplantation in the next 6 months in the treatment plan are excluded
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia
• Waldenström's macroglobulinemia or immunoglobulin M (IgM) myeloma
• Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
• Participation in an investigational therapeutic study within 3 weeks or within 5 drug half lives (t1/2) prior to first dose, whichever time is greater
• Patients known to be refractory to any proteasome inhibitor other than bortezomib or carfilzomib
• Pregnant or lactating
• History of allergy to mannitol or prior hypersensitivity to thalidomide, lenalidomide or pomalidomide
• Major surgery within 3 weeks prior to first dose,
• Prior peripheral stem cell transplant within 12 weeks of study enrollment
• Has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions or estrogen replacement therapy \[ERT\]), or any investigational therapy within 21 days of enrollment
• Myocardial infarction within 6 months prior to enrollment, New York Heart Associate (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Uncontrolled hypertension or diabetes
• Acute active infection requiring systemic antibiotics, antivirals, or anti fungals within two weeks prior to first dose

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator
• Multiple Myeloma Research Foundation: collaborator

Study Sites (5)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637-1470, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University - Karmonos Cancer Center

Detroit, Michigan, 48201, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University Health Network - Princess Margaret Cancer Center

Toronto, Ontario, MISG 2M9, Canada

Location

Related Publications (1)

• Derman BA, Zonder J, Reece D, Cole C, Berdeja J, Stefka AT, Major A, Kin A, Griffith K, Jasielec J, Jakubowiak AJ. Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. Blood Adv. 2023 Oct 10;7(19):5703-5712. doi: 10.1182/bloodadvances.2022008866.

  PMID: 36763537 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; carfilzomib; Dexamethasone; Calcium Dobesilate; daratumumab

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

• Andrzej Jakubowiak

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2012
• First Posted: August 15, 2012
• Study Start: August 13, 2012
• Primary Completion: November 14, 2025
• Study Completion: November 14, 2025
• Last Updated: December 22, 2025

Record last verified: 2025-11

Locations

CA (1); US (4)