Study of Carfilzomib, Lenalidomide, Dexamethasone and Belantamab Mafodotin in Multiple Myeloma

NCT04822337 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: IRB00081609Pro00050160LCI-HEM-NDMYE-KRDB-001
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is being done to learn if the study drug belantamab mafodotin, in combination with other standard medications, can improve multiple myeloma. This study will also help determine what effects, good and/or bad, this combination of study drugs have on subjects and their cancer, and to evaluate the overall response to this study treatment combination.

Conditions

Multiple Myeloma

Keywords

Plasma Cell Neoplasms; BCMA

Outcome Measures

Primary Outcomes (2)

• Establish Maximum Tolerated Dose (MTD)

  DLTs will be determined for each subject enrolled in Phase I as a binary variable indicating whether the subject experienced a DLT during Cycle 1 of belantamab mafodotin-containing protocol directed induction therapy.

  time to complete Cycle 1 (28 days)

• Evaluate Complete Response (CR)

  CR will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of CR or better.

  up to 5 years

Secondary Outcomes (11)

• Complete Response (CR)

  Up to 5 years

• Best Response

  Up to 5 years

• Very Good Partial Response (VGPR)

  up to 5 year

• Overall Response

  up to 5 years post treatment discontinuation

• MRD Negative

  Up to 5 years

Other Outcomes (9)

• Safety - Serious Adverse Events (SAEs)

  Up to 4-8 weeks post treatment discontinuation

• Safety - Adverse Events (AEs)

  Up to 4-8 weeks post treatment discontinuation

• Safety - Adverse Events of Special Interest (AESIs)

  Up to 4-8 weeks post treatment discontinuation

Study Arms (2)

Phase I

EXPERIMENTAL

Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

Drug: Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

Phase II

EXPERIMENTAL

Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

Drug: Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

Interventions

Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin DRUG

Phase I - Chemotherapy multiple agents systemic Phase II - Maximum Tolerated Dose from Phase I

Phase I; Phase II

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age greater than or equal to 18 years at the time of consent. Because no dosing or adverse event data are currently available on the use of belantamab mafodotin as a single agent or in combination with KRd in subjects less than 18 years of age, children are excluded from this study.
• ECOG Performance Status of less than or equal to 2
• Demonstrate adequate organ function
• Adequate cardiac function as defined by a greater than 40% left ventricular ejection fraction (LVEF) by ECHO, cardiac MRI or MUGA
• Note for subjects in phase II: if a cycle of pre-study induction therapy containing a PI or anthracycline was administered, assessment of the LVEF must be repeated.
• For those with symptomatic pulmonary disease with Grade 2 or higher symptoms (e.g. COPD, asthma) or other signs / symptoms of pulmonary disease, adequate pulmonary function as defined by a FEV1 greater than or equal to 50% of predicted and DLCO/VA greater than or equal to 50% of predicted
• Females of childbearing potential (FCBP) must have two negative serum pregnancy tests during screening: the first within 10-14 days prior to first dose of study treatment and the second within 24 hours prior to first dose of study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), are amenorrhoeic for less than 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation; or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).
• FCBP must be willing to use 2 effective contraceptive methods (at least one that is highly effective) or abstinence starting from the time of informed consent, while on belantamab mafodotin and lenalidomide. If either drug is discontinued, 2 effective forms of contraception should be continued until at least 4 weeks after the last dose of lenalidomide, and 1 form of effective contraception should be continued until 4 months post last dose of belantamab mafodotin. FCBP should use effective contraception or abstinence from consent until 30 days after last treatment with carfilzomib, and males with a partner of childbearing potential must use effective contraception or abstinence for at least 90 days post last dose of carfilzomib.
• Male subjects must agree to the following from the first dose of study treatment until 6 months after the last dose of belantamab mafodotin, to allow for clearance of altered sperm:
• Refrain from donating sperm
• PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR
• Must agree to use effective contraception/barrier as detailed below:
• Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner of reproductive potential to use an additional highly effective contraceptive method with a failure rate of less than 1% per year

You may not qualify if:

• Active infection requiring systemic therapy. NOTE: at the discretion of the treating investigator, subjects who have started antibiotic therapy for subjects who had symptoms present, symptoms must have improved to baseline or grade 1 in severity may start treatment prior to completion of their course of antibiotic therapy.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
• Subjects cannot have other prior or concomitant malignancies except for:
• Curatively treated non-melanoma skin cancer
• Other cancer for which the subject has been medically stable for at least 2 years and/or, in the opinion of the Site Principal Investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy
• Active central nervous system (CNS) involvement
• Concomitant AL amyloidosis or POEMS syndrome
• Plasma cell leukemia
• Treatment with any investigational drug within 14 days or five half-lives, whichever is shorter, prior to first dose of study treatment.
• Medical, psychiatric, or other condition/disorder (including lab abnormalities) which, in the opinion of the treating physician, would make this protocol treatment unreasonably hazardous for the subject, or could interfere with obtaining informed consent or compliance to the study procedures
• Significant cardiac disease, including any of the following:
• Greater than or equal to Class 3 New York Heart Association (NYHA) congestive heart failure (see Appendix B)
• ECG evidence of acute ischemia
• Unstable angina
• Myocardial infarction, Coronary angioplasty, stenting, or bypass grafting within three months prior to day 1 of treatment

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Amgen: collaborator
• GlaxoSmithKline: collaborator

Study Sites (2)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• Atrash S, Symanowski J, Robinson M, Flynn C, Norek S, Cox R, Plott M, Bumgarner K, Rhinehardt D, Begic X, Ndiaye AP, Robinson JD, Friend R, Paul BA, Varga C, Ferreri CJ, Pineda-Roman M, Foureau DM, Bhutani M, Voorhees PM. Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma. Blood Adv. 2026 Feb 20:bloodadvances.2025019050. doi: 10.1182/bloodadvances.2025019050. Online ahead of print.

  PMID: 41719502 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

carfilzomib; Lenalidomide; Dexamethasone; belantamab mafodotin

Condition Hierarchy (Ancestors)

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Shebli Atrash, MD, MS

  Wake Forest University Health Sciences

  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: March 26, 2021
• First Posted: March 30, 2021
• Study Start: May 19, 2021
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): November 1, 2032
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)