Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement

NCT04432714 | Recruiting Phase 1

• 1 other identifier: 2019-SR-430
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The prognosis of DLBCL with MYC rearrangement is dismal. Previous study showed that lenalidomide in combination with R-CHOP showed promising therapeutic activity and that R-DA EPOCH was superior compared to R-CHOP regimen in this cohort of patients. The investigators therefore design this phase I/II study to investigate the safety and efficacy of lenalidomide in combination with R-DA EPOCH in patients with untreated MYC-rearranged DLBCL.

Conditions

DLBCL; Untreated; MYC Gene Rearrangement

Keywords

DLBCL; MYC Gene rearrangement; Lenalidomide; R-DA EPOCH

Outcome Measures

Primary Outcomes (2)

• maximum tolerated dose and dose limited toxicity

  21 days after first cycle of R2-DA-EPOCH regimen (each cycle is 21 days)

• Overall response rate

  6 months

Secondary Outcomes (2)

• Progressive free survival

  2 years

• Overall survival

  2 years

Study Arms (1)

R2-DA-EPOCH

EXPERIMENTAL

Drug: Lenalidomide; Drug: Rituximab; Drug: Etoposide; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Prednisone

Interventions

Lenalidomide DRUG

Lenalidomide 10mg/d#15mg/d#20mg/d#25mg/d d1\~d10# 21days a cycle

R2-DA-EPOCH

Rituximab DRUG

Rituximab 375 mg/m2，IV, d0

R2-DA-EPOCH

Etoposide DRUG

Etoposide 50 mg/m2/day CI24h d1-d4

R2-DA-EPOCH

Doxorubicin DRUG

Doxorubicin 10 mg/m2/day CI24h d1-d4

R2-DA-EPOCH

Vincristine DRUG

Vincristine 0.4mg/m2/day CI24h d1-d4

R2-DA-EPOCH

Cyclophosphamide DRUG

Cyclophosphamide 750 mg/m2/day IV d5

R2-DA-EPOCH

Prednisone DRUG

Prednisone 60 mg/m2/bid oral or IV d1-d5

R2-DA-EPOCH

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Histologically confirmed DLBCL with MYC rearrangement according to WHO 2016 criteria, excluding PMBCL, PCNSL, HIV-associated lymphoma.
• ECOG PS 0-2
• Age 18-60 years old
• Expected survival ≥ 12 weeks
• A measurable or evaluable disease at the time of enrolment (diameter ≥1.5cm)
• Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Women who are pregnant or lactating. Patients have breeding intent in 12 months or cannot take effective contraceptive measures during the trial measures
• Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV infected persons
• Previous exposure to any anti-tumor therapy
• Poor hepatic and/or renal function, defined as total bilirubin, ALT, AST, Cr more than two fold of upper normal level,Ccr# 50 mL/min unless these abnormalities were related to the lymphoma
• History of DVT or PE within past 12 months
• Poor bone-marrow reserve, defined as neutrophil count less than 1.5×109/L or platelet count less than 75×109/L, unless caused by bone marrow infiltration
• New York Heart Association class III or IV cardiac failure; or Ejection fraction less than 50%;or history of following disease in past 6 months: acute coronary syndrome#acute heart failure#severe ventricular arrhythmia
• CNS or meningeal involvement
• Known sensitivity or allergy to investigational product
• Major surgery within three weeks
• Patients receiving organ transplantation
• Patients with secondary tumour, excluding cured (5 years without relapse) in situ Non-melanoma skin cancer. superficial bladder cancer, in situ cervical cancer, Gastrointestinal intramucous carcinoma and breast cancer
• Presence of Grade III nervous toxicity within past two weeks
• Active and severe infectious diseases
• Any potential drug abuse, medical, psychological or social conditions whichmay disturb this investigation and assessment

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)

Nanjing, Jiangsu, 210029, China

RECRUITING

Related Publications (3)

• Godfrey JK, Nabhan C, Karrison T, Kline JP, Cohen KS, Bishop MR, Stadler WM, Karmali R, Venugopal P, Rapoport AP, Smith SM. Phase 1 study of lenalidomide plus dose-adjusted EPOCH-R in patients with aggressive B-cell lymphomas with deregulated MYC and BCL2. Cancer. 2019 Jun 1;125(11):1830-1836. doi: 10.1002/cncr.31877. Epub 2019 Feb 1.

  PMID: 30707764 BACKGROUND

• Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):366-378. doi: 10.1182/asheducation-2016.1.366.

  PMID: 27913503 BACKGROUND

• Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, Parekh S, Lacasce A, Hayslip JW, Jagadeesh D, Nagpal S, Lechowicz MJ, Gaur R, Lucas A, Melani C, Roschewski M, Steinberg SM, Jaffe ES, Kahl B, Friedberg JW, Little RF, Bartlett NL, Wilson WH. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet Haematol. 2018 Dec;5(12):e609-e617. doi: 10.1016/S2352-3026(18)30177-7.

  PMID: 30501868 BACKGROUND

MeSH Terms

Interventions

Lenalidomide; Rituximab; Etoposide; Doxorubicin; Vincristine; Cyclophosphamide; Prednisone

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Wei Xu, M.D., Ph.D

  The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Wang, M.D., Ph.D

CONTACT

86 25 68306034; lilyw7878@163.com

Wei Xu, M.D., Ph.D

CONTACT

86 25 68306034; xuwei10000@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 16, 2020
• Study Start: June 9, 2020
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 16, 2020

Record last verified: 2020-06

Locations

CN (1)