Selinexor in Combination With Thalidomide and Dexamethasone in RRMM

NCT04891744 | Unknown Phase 1 FDA Drug

• 1 other identifier: ATG-010-IIT-MM-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma (MM) is an incurable plasma cell cancer that almost all patients eventually relapse despite advancement in treatment strategies. B-cell maturation antigen (BCMA) is a cell surface receptor that expressed primarily by malignant and normal plasma cells. This is a single-arm that includes escalation phase and expansion phase ,Selinexor in Combination withThalidomide and Dexamethasone to Treat Relapsed/Refractory Multiple Myeloma Patients.To evaluate efficacy and safety of Selinexor in combination with Thalidomide and Dexamethasone in RRMM patients received at least one prior lines of therapy

Conditions

Multiple Myeloma

Keywords

Selinexor; ATG-010; Multiple Myeloma; Relapsed/Refractory Multiple Myeloma; Thalidomide

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR in each arm: partial response (PR) + very good partial response (VGPR) + complete response (CR)

  Assessed from the date of first dose of study treatment until the date that PD assessed up to 12months

Secondary Outcomes (7)

• Duration of Response (DOR)

  12 months

• Disease Control Rate (DCR)

  12 months

• Progression-Free Survival (PFS)

  12 months

• Overall Survival (OS)

  12 months

• Minimal Residual Disease (MRD)

  12 months

Study Arms (1)

Selinexor in combination with thalidomide and Dexamethasone

EXPERIMENTAL

Selinexor in combination with thalidomide and Dexamethasone. Thalidomide will be given at 100mg/d d1-28,and Dexamethasone 20 mg/d will be given on day 1, 2,8,9,15,16,22,23. Treatment will be administered in 28-day cycles,include a total of 12 cycles. Selinexor dose escalation: 60, 80, 100mg respectively on day 1,8,15,22 for 4-week cycles. Then Selinexor will be given at the recommended dose level on phase II.

Drug: Selinexor; Drug: Thalidomide; Drug: Dexamethasone

Interventions

Selinexor DRUG

Selinexor (ATG-010# is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus along with inhibition of translation of oncoprotein mRNAs.

Also known as: ATG-010

Selinexor in combination with thalidomide and Dexamethasone

Thalidomide DRUG

100mg/d, Po. on day1-28

Also known as: fǎn yìng tíng

Selinexor in combination with thalidomide and Dexamethasone

Dexamethasone DRUG

20 mg/d Po. on day 1, 2,8,9,15,16,22,23

Also known as: Dex

Selinexor in combination with thalidomide and Dexamethasone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Known and written informed consent (ICF) voluntarily.
• Age ≥ 18 years and ≤ 75 years.
• Patients with multiple myeloma who have received first-line treatment (induction, autologous transplantation and maintenance as the same first-line treatment) and achieved at least partial remission in induction.
• At or after accepting first-line regimen, subjects must have progression disease (PD) recorded which is determined by researcher according to IMWG criteria.

You may not qualify if:

• Adequate hepatic function: total bilirubin \< 2× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of \< 3× ULN is required), AST \< 2.5× ULN, and ALT \< 2.5× ULN.
• Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculated using the formula of Cockroft-Gault).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Measurable MM as defined by at least one of the following:
• Serum M-protein (SPEP) ≥ 10 g/L
• hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
• Serum FLC ≥ 100 mg/L with abnormal FLC ratio
• Expected survival is more than 6 months.
• Adequate hematopoietic function (no blood transfusion within 2 weeks and no G-CSF/GM-CSF supportive treatment within 1 week prior to screening test):
• Hemoglobin level ≥ 80 g/L
• ANC ≥ 1,000/mm3 (1.0×109/L)
• Platelet count ≥ 75,000/mm3 (75×109/L)
• Female patients of childbearing potential must meet below two criteria:
• must agree to use effective contraception methods since signature in ICF, throughout the study and for 3 months following the last dose of study treatment.
• must have a negative serum pregnancy test at screening. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal (defined as no menstrual period for a minimum of 12 months) or permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy). A woman who is taking oral contraceptive or using intrauterine device is considered of childbearing potential.

Sponsors & Collaborators

• Li Zheng: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; Thalidomide; Dexamethasone

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)

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

• Ting Niu, M.D., Ph.D

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Li Zheng, M.D., Ph.D

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hongwei Li, MSc

CONTACT

18205191049; cpu_473lhw@126.com

Li Zheng, M.D., Ph.D

CONTACT

+86-028-85423655; lzheng2005618@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician, professor

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 18, 2021
• Study Start: July 6, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: May 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Study Protocol can be shared Starting 12 months after publication
• Access Criteria: Study Protocol must not be shared with non-participants until after publication and must be authorized by the principal investigator and sponsors

Locations

CN (1)