Ixazomib Citrate, Lenalidomide, and Dexamethasone in Treating Patients With POEMS Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 24 February 2025
• Main ID: NCT02921893
• Date of registration: 26/09/2016
• Prospective Registration: Yes
• Primary sponsor: Mayo Clinic
• Public title: Ixazomib Citrate, Lenalidomide, and Dexamethasone in Treating Patients With POEMS Syndrome
• Scientific title: Ixazomib, Lenalidomide, and Dexamethasone for Patients With POEMS Syndrome
• Date of first enrolment: October 31, 2016
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02921893
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Early Phase 1

Countries of recruitment

United States

Contacts

• Name: Angela Dispenzieri, M.D.
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Inclusion Criteria:

- POEMS syndrome requiring therapy, previously treated or untreated

- Plasma vascular endothelial growth factor (VEGF) > 2 x upper limit of normal (ULN)

- Presence of a plasma cell clone (any of the following):

- Monoclonal protein in the serum or urine

- Measurable light chains by free light chain assay

- Measurable plasmacytoma

- Monoclonal plasma cells in bone marrow

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2, or 3

- Absolute neutrophil count (ANC) >= 1000/uL obtained =< 14 days prior to registration

- Platelet count (PLT) >= 75,000/uL obtained =< 14 days prior to registration

- Total bilirubin =< 2.0 mg/dL unless due to known Gilbert's disease obtained =< 14
days prior to registration

- NOTE: If total bilirubin is > 2 mg/dL, a direct bilirubin should be performed
and must be < 1.5 mg/dL for Gilbert's to be diagnosed

- Alanine aminotransferase (ALT/serum glutamic pyruvic transaminase [SGPT]) and
aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) =<
3 x upper limit of normal (ULN) obtained =< 14 days prior to registration

- Creatinine clearance >= 30 mL/min/1.73 m^2 (as determined by Cockcroft-Gault
equation) obtained =< 14 days prior to registration

- Negative serum pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- NOTE: Females of reproductive potential must adhere to the scheduled pregnancy
testing as required in the Revlimid Risk Evaluation and Mitigation Strategy
(REMS) program

- Birth control

- Female patients of childbearing potential must be willing to use 2 methods of
birth control or be surgically sterile, or abstain from heterosexual activity
for the course of the study through 120 days after the last dose of study
medication

- NOTE: Patients of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year

- Male patients must agree to use an adequate method of contraception starting
with the first dose of study therapy through 120 days after the last dose of
study therapy

- NOTE: Abstinence is acceptable (for either males or females) if this is
the established and preferred method of contraception for the subject

- Willing to adhere to the guidelines of the Revlimid REMS (formerly known as
RevAssist) program

- NOTE: The counseling must be documented

- Provide written informed consent

- Willing to return to enrolling institution for follow-up (during the active
monitoring phase of the study)

- Note: During the active monitoring phase of a study (i.e., active treatment and
observation), participants must be willing to return to the consenting
institution for follow-up

- No contraindication to be on a minimum of 81 mg aspirin a day (or other
anticoagulant therapy as prescribed) for thromboembolism prophylaxis

- Willing to provide mandatory blood and bone marrow samples for research purposes

- Ability to complete questionnaire(s) by themselves or with assistance

Exclusion Criteria:

- Recent prior chemotherapy:

- Newly diagnosed patients (regardless of group); any prior chemotherapy for
POEMS with the following exceptions:

- Prior immunomodulators like azathioprine, cyclosporin, and/or
corticosteroids are not exclusionary therapies if used for prior diagnosis
of chronic inflammatory demyelinating polyneuropathy

- Prior chemotherapy directed at a "myeloproliferative neoplasm" like
hydroxyurea is not exclusionary

- Previously treated patients (group 2)

- Alkylators (e.g. melphalan, cyclophosphamide) =< 28 days prior to
registration

- Anthracyclines =< 28 days prior to registration

- High dose corticosteroids, immune modulatory drugs (thalidomide or
lenalidomide), or proteosome inhibitors (e.g. ixazomib or bortezomib) =<
28 days prior to registration

- Requirement for concomitant high dose corticosteroids

- EXCEPTION: Patients may be on chronic steroids (maximum dose 20 mg/day
prednisone equivalent) if they are being given for adrenal insufficiency,
rheumatoid arthritis, etc

- Receiving any other investigational agent, which would be considered as a treatment
for the primary neoplasm

- Participation in other clinical trials, including those with other investigational
agents not included in this trial, =< 30 days prior to registration and throughout
the duration of this trial

- Prior refractoriness to proteasome inhibitor or immunomodulatory drugs (IMiD)

- Any of the following because this study involves an agent that has known genotoxic,
mutagenic and teratogenic effects:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Other active malignancy =< 3 years prior to registration

- EXCEPTIONS: Non-melanotic skin cancer, ductal carcinoma in-situ, or
carcinoma-in-situ of the cervix

- NOTE: If there is a history of prior malignancy, they must not be receiving
other specific treatment for their cancer

- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens, e.g. uncontrolled infection (infection
requiring systemic antibiotic therapy or other serious infection =< 14 days prior to
registration); or uncompensated heart or lung disease

- Immunocompromised patients and patients known to be human immunodeficiency virus
(HIV) positive and currently receiving antiretroviral therapy

- Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,
carbamazepine, phenytoin, phenobarbital), or use of St. John's wort =< 14 days prior
to registration

- History of myocardial infarction =< 6 months prior to registration, or congestive
heart failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmias

- Radiotherapy =< 14 days prior to registration

- Major surgery =< 14 days prior to registration

- Failure to fully recover (i.e. =< grade 1 adverse event [AE]) from the reversible
effects of prior chemotherapy

- Known allergy to any of the study medications, their analogs, or excipients in the
various formulations of any agent

- Known gastrointestinal (GI) disease or GI procedure that could interfere with the
oral absorption or tolerance of the study drugs including difficulty swallowing

- Ongoing or active systemic infection or active hepatitis B or C virus infection


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Plasmacytoma

POEMS Syndrome

Intervention(s)

Drug: Dexamethasone

Drug: Lenalidomide

Other: Questionnaire Administration

Drug: Ixazomib Citrate

Primary Outcome(s)

Rate of normalization of VEGF defined as VEGF value decreasing to below upper limit of normal (86 pg/mL) [Time Frame: Up to 3 months]

Secondary Outcome(s)

Hematologic response rate [Time Frame: Up to 3 months]

Hematologic response rate [Time Frame: Up to 12 months]

Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [Time Frame: Up to 3 years]

Normalization of VEGF [Time Frame: Up to 12 months]

Survival time [Time Frame: Time from registration to death due to any cause, assessed up to 3 years]

Secondary ID(s)

MC1682

NCI-2016-01426

16-002976

Source(s) of Monetary Support

Please refer to primary and secondary sponsors