Selinexor Plus VRd in High Risk Newly Diagnosed Multiple Myeloma

NCT05422027 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ATG-010-IIT-MM-005
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

Brief Summary

This is a single-arm and open-label study to explore XVRd (ATG-010, Bortezomib, Lenalidomide and Dexamethasone) regimen in high-risk newly diagnosed multiple myeloma.The primary objective of the dose escalation study is to determine the safety, tolerability, and recommended phase II dose (RP2D) of selinexor; Then dose expansion at the RP2D level based on dose escalation phase will be conducted to evaluate the efficacy, safety and tolerability.The enrollment period for this study is expected to be approximately 12 months. The study will end when all patients have completed 12 cycles treatment/follow-up since the initiation of the study drug, or the last patient has expired, has been lost to follow-up, or has withdrawn consent, whichever occurs first.

Conditions

Multiple Myeloma

Keywords

Selinexor; ATG-010; Newly Diagnosed; High Risk

Outcome Measures

Primary Outcomes (3)

• Dose Escalation: Maximum Tolerated Dose (MTD)

  The MTD will be determined by study definition as the highest dose level without significant safety and tolerability concern.

  Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days) ;

• Dose Escalation: Recommended Phase 2 Does (RP2D)

  The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.

  Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days) ;

• Dose Expansion: MRD negative remission

  MRD negative remission (\<10-5) as defined by IMWG consensus

  At any time up to 12 months after XVRD treatment

Secondary Outcomes (7)

• complete response (CR)

  Cycle 1 Day 1 (each cycle consists of maximum 21 days) until a VGPR, CR or PR (up to 12 cycles)

• 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 (1)

Selinexor-VRd（XVRd）

EXPERIMENTAL

bortezomib SC 1.3mg/sqm on day 1,4,8,11, lenalidomide oral 25 mg on day 1-14, and dexamethasone 40mg on day 1,8,15 in a 21-day cycle; Selinexor dose escalation: 40，60mg respectively on day 1,8,15 for 21-days cycles. Then Selinexor will be given at the recommended dose level on phase II.

Drug: Selinexor; Drug: Bortezomib; Drug: Lenalidomide; 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. Selinexor dose escalation: 40, 60mg respectively on day 1,8,15 for 21 days cycles

Also known as: ATG-010, Xpovio

Selinexor-VRd（XVRd）

Bortezomib DRUG

The investigators gave patients subcutaneous bortezomib 1.3mg/sqm on days 1, 8,15 of a 21- day cycle. standard bortezomib-lenalidomide-dexamethasone

Also known as: Velcade

Selinexor-VRd（XVRd）

Lenalidomide DRUG

The investigators gave patients oral lenalidomide 25mg on days 1 to 14 of a 21-day cycle. standard bortezomib-lenalidomide-dexamethasone

Also known as: Revlimid

Selinexor-VRd（XVRd）

Dexamethasone DRUG

The investigators gave patients oral dexamethasone 40mg on days 1, 8, 15 of a 21-day cycle. standard bortezomib-lenalidomide-dexamethasone

Also known as: Dexamethasone Acetate

Selinexor-VRd（XVRd）

Eligibility Criteria

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

You may qualify if:

• Willing and able to written informed consent (ICF) .
• Age ≥ 18 years.
• Newly diagnosed multiple myeloma as defined by IMWG(Rajkumar, Dimopoulos et al. 2014) , measurable disease as defined IMWG 2016 criteria(Table 5) (Kumar, Paiva et al.2016), and meet at least one of the following criteria:
• Serum M-protein (SPEP) ≥ 5 g/L, If the MM type is IgA/IgD, that can be substituted by IgA/IgD quantitative level.
• hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
• Serum FLC ≥ 100 mg/L with abnormal FLC ratio ( FLC Normal ratio:0.26 to 1.65)
• According to mSMART 3.0 definition for high risk multiple myeloma:
• High Risk genetic Abnormalities t(4;14) , t(14;16) , t(14;20) , Del 17p, p53 mutation, Gain 1q
• R-ISS Stage 3
• High Plasma Cell S-phase
• GEP: High risk signature
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. ECOG PS 3 allowed, if caused by myeloma.
• Patients must have received no prior chemotherapy for multiple myeloma. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Patients must have received no prior steroid treatment for myeloma with the exception of a maximum of 14 days of treatment for symptom control.
• Adequate hepatic function: total bilirubin \< 1.5× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of \< 3× ULN is required), AST \< 2× ULN, and ALT \< 2× ULN.
• Adequate renal function: estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).

You may not qualify if:

• Patients who meet any of the following criteria will not be enrolled:
• Plasma cell leukemia.
• Documented active amyloidosis.
• Involvement of the central nervous system(CNS) by Multiple myeloma.
• Prior exposure to a SINE compound, including ATG-010.
• Currently, whether or not the patient is on medication, \> Grade 2 peripheral neuropathy or ≥ Grade ≥ 2 painful neuropathy at baseline.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and Selinexor (ATG-010) .
• Active, unstable cardiovascular function, as indicated by the presence of:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
• Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction \<40%, or
• Myocardial infarction within 6 months prior to C1D1.
• Known positive serology for HIV or HIV seropositivity.
• Known active hepatitis A, B, or C infection; eg. positive for HCV RNA or HBV-DNA.
• Women who are pregnant or nursing.

Sponsors & Collaborators

• Xia Zhongjun: lead
• Antengene Corporation: collaborator

Study Sites (4)

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510000, China

NOT YET RECRUITING

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China,

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

NOT YET RECRUITING

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; Bortezomib; Lenalidomide; Dexamethasone; dexamethasone acetate

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)

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

Study Officials

• Zhongjun Xia, Ph.D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhongjun Xia, Ph.D

CONTACT

+86-020-87342438; xiazhj@sysucc.org.cn

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: June 13, 2022
• First Posted: June 16, 2022
• Study Start: July 25, 2022
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: June 17, 2024

Record last verified: 2024-06

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 (4)