Tazemetostat Plus CHOP in 1L T-cell Lymphoma

NCT06692452 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 24-462
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This research is being done to evaluate tazemetostat in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as a possible treatment for peripheral T-Cell Lymphoma (PTCL). The name of the study drugs involved in this study are:

• Tazemetostat (a type of inhibitor for Enhancer of Zeste Homolog 2 (EZH2))
• Standard of care CHOP therapy:
• Cyclophosphamide (a type of alkylating agent)
• Doxorubicin (a type of anthracycline antibiotic)
• Vincristine (a type of vinca alkaloid)
• Prednisone (a type of corticosteroid)
• Standard of care BEAM conditioning regimen for autologous stem cell transplant:
• Carmustine (a type of alkylating agent)
• Etoposide (a type of Topoisomerase II inhibitor)
• Cytarabine (a type of antineoplastic)
• Melphalan (a type of alkylating agent)

Conditions

Lymphoma; Peripheral T Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Keywords

Lymphoma; Peripheral T-cell Lymphoma; PTCL; Angioimmunoblastic T-cell Lymphoma; AITL; Enteropathy-Associated T-Cell Lymphoma; EATL; Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma; MEITL

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  CRR rate was defined as the proportion of participants who achieved CR during the first six cycles of treatment.

  Up to 18 weeks

Secondary Outcomes (6)

• Median Overall Survival (OS)

  Up to 5.5 years

• Median Progression Free Survival (PFS)

  Up to 1.5 years

• Duration of Response (DOR)

  Up to 1.5 years

• Grade 3-5 Treatment-Related Toxicity Rate

  Up to 3.5 years

• Transplant Rate

  Up to 1.5 years

Study Arms (2)

Tazemetostat + CHOP Therapy + Transplant Elected

EXPERIMENTAL

Enrolled participants will complete: * Baseline visit * Prephase Period: Days -14 through -1: Predetermined dose of Tazemetost 2x daily * Induction Period: Cycles 1 through 6 (21 day cycles): * Cycle 1 Day 1: tumor biopsy and CT scan * Day 1: Predetermined dose of Cyclophosphamide once, Doxorubicin once, and Vincristine once * Days 1 through 5: Predetermined dose of Prednisone 1x daily * Days 2 through 21: Predetermined dose of Tazemetost 2x daily * Prior to Cycle 4 Day 1: Pet-CT scan * Note, treatment will stop if participants do not respond to the drugs after the first 3 cycles * Bone marrow biopsy and Pet-CT scan at end of Cycle 6 * Maintenance Period: * Day 0: autologous stem cell transplant with BiCNU, Etoposide, Cytarabine, and Melphalan (BEAM) * Day 100: PET-CT scan * Cycles 1 through 6 (28 day cycles): --Days 1 through 28: Predetermined dose of Tazemetost 2x daily * After Cycle 3: CT scan * Cycle 4 Day 1: CT scan * End of treatment visit * Follow up is for 4 years

Drug: Tazemetostat; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Cytoxan; Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan

Tazemetostat + CHOP Therapy + Transplant Not Elected

EXPERIMENTAL

Enrolled participants will complete: * Baseline visit * Prephase Period: Days -14 through -1: Predetermined dose of Tazemetost 2x daily * Induction Period: Cycles 1 through 6 (21 day cycles): * Cycle 1 Day 1: tumor biopsy and CT scan * Day 1: Predetermined dose of Cyclophosphamide once, Doxorubicin once, and Vincristine once * Days 1 through 5: Predetermined dose of Prednisone 1x daily * Days 2 through 21: Predetermined dose of Tazemetost 2x daily * Prior to Cycle 4 Day 1: Pet-CT scan * Note, treatment will stop if participants do not respond to the drugs after the first 3 cycles * Pet-CT scan at end of Cycle 6. * Maintenance Period: * Cycles 1 through 6 (28 day cycles): --Days 1 through 28: Predetermined dose of Tazemetost 2x daily. * After Cycle 3: CT scan * Cycle 4 Day 1: CT scan * End of treatment visit * Follow up is for 4 years

Drug: Tazemetostat; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Cytoxan

Interventions

Tazemetostat DRUG

EZH2 inhibitor, 200 mg tablet, taken orally per protocol.

Also known as: Tazverik, [1,1'-Biphenyl]-3-carboxamide,N-[(1,2-dihydro- 4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-5- [ethyl(tetrahydro-2H-pyran-4-yl)amino]-4-methyl- 4'-(4-morpholinylmethyl)-, hydrobromide (1:1)

Tazemetostat + CHOP Therapy + Transplant Elected; Tazemetostat + CHOP Therapy + Transplant Not Elected

Doxorubicin DRUG

Anthracycline antibiotic, 10, 20, 50, 100, and 200 mg vials, via intravenous (into the vein) infusion per institutional standard of care.

Also known as: Hydroxydaunorubicin

Tazemetostat + CHOP Therapy + Transplant Elected; Tazemetostat + CHOP Therapy + Transplant Not Elected

Vincristine DRUG

Vinca Alkaloid, 1, 2, and 5mL vials, via intravenous (into the vein) infusion per institutional standard of care.

Also known as: Oncovin

Tazemetostat + CHOP Therapy + Transplant Elected; Tazemetostat + CHOP Therapy + Transplant Not Elected

Prednisone DRUG

Corticosteroid, 1, 2.5, 5, 10, 20, 25, and 50 mg tablets, taken orally per institutional standard of care.

Also known as: Prednisolone

Tazemetostat + CHOP Therapy + Transplant Elected; Tazemetostat + CHOP Therapy + Transplant Not Elected

Cytoxan DRUG

Alkylating agent, 100mg, 200 mg, and 500mg vials, and 1 and 2 gram vials, via intravenous (into the vein) infusion per institutional standard of care.

Also known as: Cyclophosphamide, Cyclophosphamide-OE

Tazemetostat + CHOP Therapy + Transplant Elected; Tazemetostat + CHOP Therapy + Transplant Not Elected

Carmustine DRUG

Alkylating agent, 100 mg single dose vials, via intravenous (into the vein) infusion per institutional standard of care.

Also known as: BiCNU

Tazemetostat + CHOP Therapy + Transplant Elected

Etoposide DRUG

Topoisomerase II inhibitor, 100mg single dose vial, via intravenous (into the vein) infusion per institutional standard of care.

Also known as: Etopophos

Tazemetostat + CHOP Therapy + Transplant Elected

Cytarabine DRUG

Antineoplastic, 20mg single dose vial, via intravenous, intrathecal, or subcutaneous injection per institutional standard of care

Tazemetostat + CHOP Therapy + Transplant Elected

Melphalan DRUG

Alkylating agent, 90 mg multi-dose vial, via parenteral infusion per institutional standard of care.

Tazemetostat + CHOP Therapy + Transplant Elected

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed peripheral T cell lymphoma of one of the following subtypes: PTCL-NOS, Follicular helper T-cell lymphoma (ICC 2022) or Nodal T-follicular helper (TFH) cell lymphoma by (WHO 2022) which includes follicular helper T-cell lymphoma, AITL and follicular helper T cell lymphoma, follicular type, EATL, MEITL. All pathology will be reviewed at BWH. BWH review is not required prior to enrollment and patients may be enrolled based upon local pathology analysis. Ten blank slides will be required from outside tumor biopsy for correlative studies.
• No prior treatment for T NHL with the exception of one cycle of CHOP or CHOEP or 7 days of corticosteroids at a dose of up to prednisone 60 mg or equivalent for palliation of disease related symptoms so long as the corticosteroids are discontinued prior to tazemetostat prephase or cycle 1 of treatment if not receiving the prephase.
• At least one bi-dimensionally measurable lesion, defined as \>1.5 cm in its longest dimension as measured by CT.
• Age ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL (750 mcl if bone marrow involvement with lymphoma)
• platelets ≥75,000/mcL (25,000 if bone marrow involvement with lymphoma)
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• creatinine ≤ 1.5 x institutional ULN OR
• glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2
• Because the effects of tazemetostat on human immunodeficiency virus (HIV)-infected participants and anti-retroviral therapy is unknown, patients with known HIV infection are not eligible for this trial.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment, are not eligible.

You may not qualify if:

• Participants who have had chemotherapy for T cell lymphoma prior to entering the study (except 1 cycle of CHOP/CHOEP as noted above). Prior radiotherapy may be allowed after discussion with the sponsor-investigator so long as the area radiated was not the only measurable site of disease.
• Participants who are receiving any other investigational agents.
• Patients with known central nervous system involvement with lymphoma
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat or other agents used in study.
• Prior organ transplantation.
• Current motor or peripheral neuropathy with grade \>1.
• History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions include:
• Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible.
• Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for \> 2 years prior to enrollment are eligible.
• Patients with low-grade, early-stage prostate cancer (Gleason score 6, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible.
• Uncontrolled intercurrent illness.
• Pregnant women and women intending to become pregnant are excluded from this study because chemotherapeutic agents used in this study have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tazemetostat, breastfeeding should be discontinued if the mother is treated with tazemetostat.
• Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 2 weeks before the start of Cycle 1.

Sponsors & Collaborators

• Eric Jacobsen, MD: lead
• Ipsen: collaborator

MeSH Terms

Conditions

Lymphoma; Lymphoma, T-Cell, Peripheral; Immunoblastic Lymphadenopathy; Enteropathy-Associated T-Cell Lymphoma

Interventions

tazemetostat; Doxorubicin; Vincristine; Prednisone; Prednisolone; Cyclophosphamide; Carmustine; Etoposide; etoposide phosphate; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Eric Jacobsen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

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: Sponsor Investigator

Study Record Dates

• First Submitted: November 15, 2024
• First Posted: November 18, 2024
• Study Start: December 24, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2032
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)