Relapsed/Refractory Malignant Lymphomas Clinical Trial
— BeEAC-1Official title:
A Phase II, Multicenter, Prospective, Non-randomised, Open-label, Clinical Trial to Evaluate Effectiveness and Safety of BeEAC Conditioning Regimen in Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation
Nowadays there is no randomized trials for comparison the effectiveness and tolerability of
different conditioning regimens.
Bendamustine is a unique chemotherapeutic agent that combines alkylating action of nitrogen
mustard and the activity of purine antimetabolite. Bendamustine has shown its effectiveness
for the treatment of patients with chronic lymphoproliferative diseases such as chronic
lymphocytic leukemia and several indolent lymphomas. The literature also presents evidence of
the effectiveness bendamustine in patients with Hodgkin's lymphoma who received multiple
lines of prior chemotherapy, including high dose chemotherapy and transplantation of
peripheral hematopoietic stem cells. There are also data of using bendamustine as a part of
conditioning regimen.
In this context, it was planned a study for evaluation the safety and effectiveness of the
BeEAC (bendamustine, etoposide, cytarabine, cyclophosphamide) conditioning regimen prior to
autologous transplantation of peripheral hematopoietic stem cells for the treatment of
relapsed/refractory malignant lymphomas.
| Status | Recruiting |
| Enrollment | 100 |
| Est. completion date | December 31, 2020 |
| Est. primary completion date | December 31, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Be willing and able to provide written informed consent for the trial 2. Be = 18 years of age on day of signing informed consent 3. Eastern Cooperative Oncology Group (ECOG) < 2. 4. Relapsed/refractory malignant lymphoma patients with indications to autologous hematopoietic stem-cell transplantation Exclusion Criteria: 1. Participation in another clinical trials 2. Clinically relevant heart disease: - Myocardial infarction during previous 6 months - Unstable angina during previous 3 months - Congestive heart failure (III-IV NYHA) - Clinically relevant ventricular arrhythmias - corrected QT interval (QTc) > 460 ?? on ECG (calculated using Frederics formula) - Left ventricular ejection fraction = 45% on Echocardiogram - Atrial Hypotension (systolic pressure < 86 mmHg) or bradycardia (< 50 per minute, exclusion - drug-induced bradycardia) - Uncontrolled arterial hypertension (systolic pressure > 170 mmHg or diastolic pressure > 105 mmHg) 3. Severe renal dysfunction (serum creatinine > 250 µmol/l) 4. Severe hepatic dysfunction (total bilirubin > 40 µmol/l) 5. Known history of Human Immunodeficiency Virus or active Hepatitis B and C 6. Psychiatric or substance abuse disorders that would interfere with the cooperation with the requirements of the trial 7. Hypersensitivity to investigational drugs 8. Pregnant or breastfeeding females or males and females with childbearing potential must be willing to use an adequate method of birth control (intrauterine device, vasectomy of female subjects' male partner, contraceptive rod implanted into the skin, combination method - (requires use of two of the following) diaphragm with spermicide, cervical cap spermicide, contraceptive sponge, condom, hormonal contraceptive) |
| Country | Name | City | State |
|---|---|---|---|
| Russian Federation | The Federal Budget-Funded Institution National Medical Surgical Center named after N. I. Pirogov of the Ministry of health of the Russian Federation | Moscow |
| Lead Sponsor | Collaborator |
|---|---|
| State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia |
Russian Federation,
Blay J, Gomez F, Sebban C, Bachelot T, Biron P, Guglielmi C, Hagenbeek A, Somers R, Chauvin F, Philip T. The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group. Blood. 1998 Nov 15;92(10):3562-8. — View Citation
Chen YB, Lane AA, Logan B, Zhu X, Akpek G, Aljurf M, Artz A, Bredeson CN, Cooke KR, Ho VT, Lazarus HM, Olsson R, Saber W, McCarthy P, Pasquini MC. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015 Jun;21(6):1046-1053. doi: 10.1016/j.bbmt.2015.02.005. Epub 2015 Feb 14. — View Citation
Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. doi: 10.1200/JCO.2007.12.5070. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. — View Citation
Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Merkle K, Montillo M. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012 Oct;159(1):67-77. doi: 10.1111/bjh.12000. Epub 2012 Aug 4. — View Citation
Martino M, Olivieri A, Offidani M, Vigna E, Moscato T, Fedele R, Montanari M, Console G, Gentile M, Messina G, Irrera G, Morabito F. Addressing the questions of tomorrow: melphalan and new combinations as conditioning regimens before autologous hematopoietic progenitor cell transplantation in multiple myeloma. Expert Opin Investig Drugs. 2013 May;22(5):619-34. doi: 10.1517/13543784.2013.788643. Epub 2013 Apr 4. Review. — View Citation
Moskowitz AJ, Hamlin PA Jr, Perales MA, Gerecitano J, Horwitz SM, Matasar MJ, Noy A, Palomba ML, Portlock CS, Straus DJ, Graustein T, Zelenetz AD, Moskowitz CH. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2013 Feb 1;31(4):456-60. doi: 10.1200/JCO.2012.45.3308. Epub 2012 Dec 17. — View Citation
Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Müller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V; German Hodgkin's Lymphoma Study Group; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15;359(9323):2065-71. — View Citation
Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. doi: 10.1182/blood-2011-04-351924. Epub 2011 Aug 3. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence of Treatment-Emergent Adverse Events | The primary safety analysis will be based on subjects who experienced toxicities as defined by CTCAE criteria. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received BeEAC including serious adverse events (SAEs). Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to NCI CTCAE 4.03. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading and action taking with regard to trial treatment (Incidence of Treatment-Emergent Adverse Events). |
From admission till discharge from the hospital (approximately 30 days) | |
| Secondary | Overall Survival | 2 years | ||
| Secondary | Progression-Free Survival | 2 years | ||
| Secondary | Retrospective Comparison of Overall Survival between Carmustine, Etoposide, Cytarabine, Melphalan (BEAM), Cyclophosphamide, Carmustine, Etoposide(CBV) and BeEAC conditioning regimens | The analysis will be based on comparison of overall survival between different conditioning regimens | 2 years | |
| Secondary | Retrospective Comparison of Progression-Free Survival between Carmustine, Etoposide, Cytarabine, Melphalan (BEAM), Cyclophosphamide, Carmustine, Etoposide(CBV) and BeEAC conditioning regimens | The analysis will be based on comparison of Progression-Free survival between different conditioning regimens | 2 years |