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New Genotype-guided Treatment in Newly Diagnosed PTCL

ConditionPeripheral T-cell Lymphoma (PTCL)
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorRuijin Hospital

About this trial

This is a phase I/II study evaluate the safety and efficacy targeted agents in combination with standard CHOP in new genotypic subtypes in treatment naive peripheral T-cell lymphoma. Phase I is to confirm RP2D of targeted agent. Phase II is a multicenter, prospective, randomized, open-label, controlled design to evaluate the efficacy and safety of new genotype-guided targeted agents plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-X2) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with peripheral T-cell lymphoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically-confirmed Peripheral T-cell lymphoma

Availability of archival or freshly collected tumor tissue before study enrollment enough for NGS

Evaluable lesion by PET-CT or CT scan

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

Disqualifiers

Patients with ALCL and cutaneous TCL, MEITL, HSTCL, T-PLL, etc.

Patients with central nervous system (CNS) lymphoma

History of malignancies except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases

Trial design

Design model

Parallel

Treatments tested in this trial

  • Azacitidine plus Selinexor with CHOP

    Drug

    Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 for the first cycle. If tumor NGS indicates TP53-mutated genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive azacitidine d-5 to d-1 and Selinexor 40mg qw combined with standard CHOP.

  • Decitabine plus Selinexor with CHOP

    Drug

    Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 for the first cycle. If tumor NGS indicates TP53-mutated genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive Decitabine RP2D (confrimed by phase I) and Selinexor 40mg qw combined with standard CHOP.

  • Zeprumetostat plus chidamide with CHOP

    Drug

    Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 for the first cycle. If tumor NGS indicates core epigenetic genes-mutated genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive Zeprumetostat RP2D (confrimed by phase I) and chidamide 20mg biw combined with standard CHOP.

  • Azacitidine plus Golidocitinib with CHOP

    Drug

    Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 for the first cycle. If tumor NGS indicates other genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive Azacitidine ih d-5-d-1 and Golidocitinib RP2D (confirmed by Phase I) combined with standard CHOP.

  • CHOP

    Drug

    Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 for cycle 1 to cycle 6.

Treatment groups

108 Participants
are divided into 4 treatment groups
Group A: Subgroup 1Experimental treatment 2 interventions
Group B: Subgroup 2Experimental treatment 2 interventions
Group C: Subgroup 3Experimental treatment 2 interventions
Group D: Subgroup 4Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Recommended Phase 2 Dose (RP2D) for Phase I

: Recommended Phase 2 Dose (RP2D) for Phase I of oral targeted agents in each genetic subtypes by BOIN methods

Time frame
Dose Limiting Toxicity (DLT) time window (28 days from Cycle 2)
2

Complete response rate (CRR) for Phase II

Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.

Time frame
End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days])

Secondary outcomes

1

Progression-free survival

Progression-free survival was defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.

Time frame
Baseline up to data cut-off (up to approximately 2 years)
2

Overall survival

Overall survival was defined as the time from the date of randomization to the date of death from any cause.

Time frame
Baseline up to data cut-off (up to approximately 2 years)
3

Overall response rate (ORR)

Percentage of participants with complete and partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.

Time frame
End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days])
4

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame
From enrollment to study completion, a maximum of 4 years

Other outcomes

Sponsors and contacts

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

Ruijin Hospital

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: