Treatment of POEMS Syndrome With Daratumumab

NCT04396496 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 207442
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This trial investigates the use of Daratumumab (DARA), an antibody directed at the human cluster of differentiation 38 (CD38) molecule, for the treatment of patients with Polyneuropathy, Organomegaly, Endocrinopathy, m Protein Component, Skin Changes (POEMS) syndrome. This trial will enroll ten subjects, who will complete 12 four-week cycles of DARA, in combination with the immunomodulatory drug (IMiD) lenalidomide. Objectives of this study include improvement in neuropathy and performance status, as well as improvement in laboratory values and survival.

Conditions

POEMS Syndrome

Outcome Measures

Primary Outcomes (1)

• Treatment Success

  There is a one-point improvement in ECOG performance score; and/or ≥ 50% reduction in ONLS score at Day 360.

  360 days

Study Arms (1)

Daratumumab Injection

EXPERIMENTAL

Up to 12 four-week cycles of Daratumumab (DARA), in combination with the immunomodulatory drug (IMiD) lenalidomide. DARA is injected. Dosage calculated by weight.On Cycles 1 and 2, DARA is given on Days 1, 8,15 and 22. On Cycles 3-6,DARA is given on Days 1 and 15. On Cycles 7-12, DARA is given on Day 1. Lenalidomide is taken by mouth. 15 mg on Days 1-21 of each cycle.

Drug: Daratumumab Injection

Interventions

Daratumumab Injection DRUG

DARA is a human monoclonal antibody that specifically recognizes the CD38 molecule that is expressed at a high level in a variety of hematological malignancies, including myeloma cells. DARA injection will be given with oral lenalidomide for up to 12 four week cycles.

Also known as: Darzalex

Daratumumab Injection

Eligibility Criteria

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

You may qualify if:

• Patients must have POEMS syndrome and meet the diagnostic criteria for POEMS syndrome as described in Appendix I.
• Patients must have a platelet count of ≥ 50,000/μL.
• Patients must be at least 18 years of age.
• Participants must have preserved renal function as defined by a serum creatinine level of \< 3 mg/dL.
• Participants must have an ejection fraction by echocardiogram (ECHO) or multigated acquisition (MUGA) scan ≥ 40 percent.
• Eastern Cooperative Oncology Group ≥ 1,
• Overall Neuropathy Limitations Scale (ONLS) ≥ 1.
• Patients must have signed an institutional review board (IRB)-approved informed consent indicating their understanding of the proposed treatment and understanding that the protocol has been approved by the IRB.

You may not qualify if:

• Documented allergy to lenalidomide, DARA, mannitol, other monoclonal antibodies or human proteins and mammalian-derived products.
• Prior treatment with DARA or other CD38 monoclonal antibodies
• Patients with central nervous system (CNS) Multiple Myeloma (MM) involvement.
• Patients who have received an investigational drug or device within 4 weeks prior to enrollment or received live attenuated vaccine within 4 weeks prior to enrollment.
• Poorly controlled hypertension, diabetes mellitus, or other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
• Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be accepted if the patient's life expectancy exceeds five years.
• Male and Female subjects and their partners of reproductive potential may not participate unless they have agreed to use an effective contraceptive while on study and for 3 months after cessation of DARA.
• Males who are unwilling to abstain from sperm donation while on study and for 3 months after cessation of DARA.
• Females of childbearing potential must have a negative pregnancy test documented within one week of registration.
• Females who are pregnant or nursing women may not participate.
• Patients with POEMS syndrome, who do not have disseminated bone marrow (BM) involvement and have an isolated plasmacytoma; these patients should be considered for irradiation.
• Subjects has had major surgery within 2 weeks prior to enrollment.
• Clinically significant cardiac disease, including myocardial infarction within the past 6 months or unstable or uncontrolled conditions (e.g., unstable angina or congestive heart failure) or other cardiac disease which in the opinion of the investigator would constitute a hazard for participating in the study. Some cardiac dysfunction is expected in this population.
• Participant has known chronic obstructive pulmonary disease (COPD) \[defined as a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal, forced vital capacity (FVC), etc.\] and diffusion capacity (DLCO) \< 40% of predicted.), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed). Exception may be granted if the principal investigator documents that the patient is a candidate for therapy since alternative therapies will at least have similar or not more toxicity.
• Participant with known or suspected COPD must have an FEV1 test during screening.

Sponsors & Collaborators

• University of Arkansas: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Conditions

POEMS Syndrome

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Beth Scanlan
• Organization: University of Arkansas for Medical Sciences

bscanlan@uams.edu

5016868274

Study Officials

• Frits van Rhee, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 20, 2020
• Study Start: September 22, 2020
• Primary Completion: August 29, 2023
• Study Completion: October 16, 2023
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2023-10

Locations

US (1)