ATG-010(Selinexor) in Combination With Chemotherapy in RRMM

NCT04877275 | Unknown Phase 2 FDA Drug

• 1 other identifier: ATG-010-IIT-MM-002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

This is a single-arm that includes two experimental arms,Selinexor(ATG-010) in Combination with Chemotherapy to Treat Relapsed/Refractory Multiple Myeloma Patients.To evaluate efficacy and safety of ATG-010 in combination with chemotherapy in RRMM patients received at least one prior lines of therapy

Conditions

Multiple Myeloma

Keywords

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

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)

• Minimal Residual Disease (MRD)

  12 months

• Overall Survival (OS)

  12 months

• Progression-Free Survival (PFS)

  12 months

• Duration of Response (DOR)

  12 months

• Clinical Benefit Rate (CBR)

  12 months

Study Arms (2)

Arm I: Selinexor+Pegylated liposomal doxorubicin +Dexamethasone

EXPERIMENTAL

Arm I is given XDd regimen (ATG-010(Selinexor) 80mg/d QW, Pegylated liposomal doxorubicin 25mg/m2, d1and Dexamethasone 40mg/d QW) in approximately 25 subjects. 4 weeks per cycle and include a total of 12 cycles.

Drug: Selinexor (80mg/d); Drug: Pegylated liposomal doxorubicin; Drug: Dexamethasone

Arm II: Selinexor+Cyclophosphamide+Dexamethasone

EXPERIMENTAL

Arm II is given XCd regimen (ATG-010 100mg/d QW, Cyclophosphamide 300mg/m2, d1and Dexamethasone 40mg/d QW). 4 weeks per cycle and include a total of 12 cycles.

Drug: Selinexor (100mg/d); Drug: Dexamethasone; Drug: Cyclophosphamide

Interventions

Selinexor (80mg/d) 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. Arm I：80mg/d QW ;

Also known as: ATG-010

Arm I: Selinexor+Pegylated liposomal doxorubicin +Dexamethasone

Selinexor (100mg/d) 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. Arm II：100mg/d QW ;

Also known as: ATG-010

Arm II: Selinexor+Cyclophosphamide+Dexamethasone

Pegylated liposomal doxorubicin DRUG

25 mg/m\^2 intravenously on day 1 , QW

Also known as: PLD

Arm I: Selinexor+Pegylated liposomal doxorubicin +Dexamethasone

Dexamethasone DRUG

Dexamethasone 40mg/d QW

Also known as: Dex

Arm I: Selinexor+Pegylated liposomal doxorubicin +Dexamethasone; Arm II: Selinexor+Cyclophosphamide+Dexamethasone

Cyclophosphamide DRUG

Cyclophosphamide：300mg/m2, d1 QW，

Also known as: CTX

Arm II: Selinexor+Cyclophosphamide+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:

• Left ventricular ejection fraction（LVEF ）≥50% by an echocardiogram or MUGA scan in 42 days before the first administration
• 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) ≥ 5 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 platelet transfusion within 2 weeks prior to screening test):
• Hemoglobin level ≥ 60 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.

Sponsors & Collaborators

• Chunyan Sun, MD: lead

Study Sites (5)

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

NOT YET RECRUITING

The First Affiliated Hospital of Air Force Medical University

Xi’an, Shanxi, 710000, China

NOT YET RECRUITING

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, 710004, China

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; liposomal doxorubicin; 1-dodecylpyridoxal; Dexamethasone; Cyclophosphamide

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Chunyan Sun, M.D., Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunyan Sun, M.D., Ph.D

CONTACT

13237183940; suncy0618@163.com

Hongwei Li, MSc

CONTACT

18205191049; cpu_473lhw@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician, professor

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 7, 2021
• Study Start: May 21, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: December 6, 2023

Record last verified: 2023-12

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 (5)