Clinical trial NCT03795571: Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone in Relapse and Refractory DLBCL
Official title: Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone (R2-GOD) in Treatment of Relapse/Refractory DLBCL:A Phase I Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Diffuse Large B-cell Lymphoma Recurrent
Diffuse Large B Cell Lymphoma Refractory
Keywords: lenalidomide
R-GOD
DLBCL
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2019-01-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Previous study showed that Lenalidomide or R-GDP could achieve response in Relapse and Refractory DLBCL.The investigators therefore design this phase I study to investigate the safety and efficacy of R2-GOD in relapsed diffuse large-cell lymphoma.


Eligibility criteria: Inclusion Criteria:

* Age 18-65 years old;
* ECOG PS 0- 2;
* Histologically confirmed diffuse large B cell lymphoma（With exception of Primary mediastinal large B cell lymphoma、Primary central nervous system lymphoma、HIV-related lymphoma),relapse or refractory,defined as:

  * relapse after standard first-line immunochemotherapy( R-CHOP or R-CHOP like)
  * SD as best response after 4 cycles or PD after 2 cycles of first-line immunochemotherapy;
* a measurable or evaluable disease at the time of enrollment(diameter ≥ 1.5cm）；
* Eligible for subsequent autologous stem cell transplantation；
* Female subjects in childbearing age, their serum or urine pregnancy test must be negative. All patients must agree to take effective contraceptive measures during the trial measures
* Expected survival ≥ 12 weeks；
* Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

* Women who are pregnant or lactating. Patients have breeding intent in 12 months or cannot take effective contraceptive measures during the trial measures；
* Uncontrollable active infection within four week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons；
* Used of systemic anti-tumor treatment within four weeks；
* CNS or meningeal involvement;
* 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;
* 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；
* Known sensitivity or allergy to investigational Product;
* Major surgery within three weeks;
* Presence of Grade III nervous toxicity within past two weeks;
* Active and severe infectious diseases;
* History of DVT or PE within past 12 months；
* Any potential drug abuse, medical, psychological or social conditions which may disturb this investigation and assessment;
* In any conditions which investigator considered ineligible for this study.

Primary outcomes:
measure: maximum tolerated dose and dose limited toxicity
timeFrame: 28 days after first cycle of R2-GOD regimen
Secondary outcomes:
measure: Overall response rate,
timeFrame: 6 months
measure: Progressive free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital
state: Jiangsu
Study officials:
affiliation: The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
name: Wei Xu, PhD& MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. doi: 10.1111/bjh.12846. Epub 2014 Mar 25.
citation: Martin A, Redondo AM, Dlouhy I, Salar A, Gonzalez-Barca E, Canales M, Montes-Moreno S, Ocio EM, Lopez-Guillermo A, Caballero D; Spanish Group for Lymphomas and Autologous Bone Marrow (GELTAMO). Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 1b study from GELTAMO group. Br J Haematol. 2016 Apr;173(2):245-52. doi: 10.1111/bjh.13945. Epub 2016 Feb 5.
citation: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. doi: 10.1200/JCO.2013.53.9593. Epub 2014 Sep 29.
citation: Shen QD, Zhu HY, Wang L, Fan L, Liang JH, Cao L, Wu W, Xia Y, Li JY, Xu W. Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial. Lancet Haematol. 2018 Jun;5(6):e261-e269. doi: 10.1016/S2352-3026(18)30054-1. Epub 2018 May 8.