Selinexor in Combination With MTX+Ritu to Treat R/R CNSL

ConditionCentral Nervous System Lymphoma

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorTong Chen, MD

About this trial

This is a single-arm and open-label study to explore X+MTX+Ritu (ATG-010, Methotrexate, Rituximab) regimen in Relapse refractory PCNSL patients. Approximately 30 patients will be enrolled in the study. In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen and escalating doses of oral ATG-010 weekly in a 3+3 design. Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must be able to understand and be willing to sign a written informed consent document.

Men and woman who are 18-75 years old on the day of consenting to the study.

Histologically documented PCNSL and SCNSL secondary to histologically documented systemic diffuse large B-cell lymphoma (DLBCL).

Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL.

Disqualifiers

Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.

Lymphoma patients with only intraocular involvement.

Pathological diagnosis of PCNSL is T-cell lymphoma.

Patients with disease progression within 6 months of prior methotrexate-containing regimen.

Trial design

Design model

Single group

Treatments tested in this trial

Selinexor
Drug
Selinexor dose escalation: 60,80,100mg respectively on day 1,8,15,22 for 28 days cycles, and dose expansion at the RP2D of Selinexor. PR patients after induction treatment will continue ATG-010 maintenance up to 1 year or until disease progression, intolerable toxicity, death.
Rituximab
Drug
Rituximab 375 mg/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.
Methotrexate
Drug
high-dose Methotrexate 3.5 g/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.

Treatment groups

30 Participants

are divided into 1 treatment group

Group A: X-MTX-RituExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

Dose Escalation: Maximum Tolerated Dose (MTD) of Selinexor

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

Time frame

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

Dose Escalation: Recommended Phase 2 Does (RP2D) of Selinexor

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 data collected during the dose escalation portion of the study

Time frame

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

Objective Response Rate (ORR)

ORR is defined as the proportion of patients with a best response of Complete remission (CR) or Unconfirmed(CRu), or PR during induction therapy

Time frame

Cycle 1 Day 1 (each cycle consists of maximum 21 days) until a CR, CRu or PR (up to 18 cycles(each cycle is 21 days)).

Secondary outcomes

Duration of Response (DOR)

Duration from the first observation of at least PR to time of progressive disease(PD), or deaths due to disease progression,whichever occurs first

Time frame

From first dose of study drug administration to end of treatment, up to 18 cycles(each cycle is 21 days)

Overall Survival (OS)

Occurrence of death regardless of cause

Time frame

up to 12 months

Progression-Free Survival (PFS)

Duration from start of study treatment to PD or death (regardless of cause), whichever comes first

Time frame

up to 12 months

Number of Participants with Adverse Events

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Time frame

From first dose of study drug administration to end of treatment (up to 18 cycles(each cycle is 21 days))

Other outcomes

Gene mutations and frequency of 475 gene and whole exon

The types of gene mutations and frequency of tumor are measured by whole exon sequencing via NGS(next-generation sequencing).

Time frame

At baseline

The concentration of interleukin-10(IL-10)，interleukin-6(IL-6)，CXCL-13 cytokine in cerebrospinal fluid(CSF)

The levels of cytokines will be analyzed by flow cytometry

Time frame

At the baseline, day 1 at cycle 3, 5 (21 days/cycle), and every 3 months in the maintenance stage (up to 1 year))

Circulating tumor DNA (ctDNA) in the CSF

The levels of ctDNA will be analyzed by next-generation sequencing.

Time frame

At the baseline, day 1 at cycle 3, 5 (21days/cycle), and every 3 months in the maintenance stage (up to 1 year))

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Tong Chen, MD

Lead sponsor

Huashan Hospital

Sponsor institution

Antengene Corporation

Collaborator

Source ClinicalTrials.gov

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