BeEAC Conditioning Regimen in Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation

NCT ID: NCT03315520

Last Updated: 2018-05-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-22

Study Completion Date

2020-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Relapsed/Refractory Malignant Lymphomas

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Relapsed/refractory malignant lymphomas

Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation using BeEAC (Bendamustine, Cytarabine, Etoposide, Cyclophosphamide) conditioning regimen

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

BeEAC conditioning regimen:

bendamustine 200 mg/м2 D-6 - D-5; cytarabine 400 mg/м2 D-4 - D-1; etoposide 400 mg/м2 D-4 - D-1; cyclophosphamide 140 mg/м2 totally, divided in 4 days (D-4 - D-1)

Interventions

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Bendamustine

BeEAC conditioning regimen:

bendamustine 200 mg/м2 D-6 - D-5; cytarabine 400 mg/м2 D-4 - D-1; etoposide 400 mg/м2 D-4 - D-1; cyclophosphamide 140 mg/м2 totally, divided in 4 days (D-4 - D-1)

Intervention Type DRUG

Other Intervention Names

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Cytarabine Etoposide Cyclophosphamide

Eligibility Criteria

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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 мс 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vladislav Sarzhevskiy, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Locations

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The Federal Budget-Funded Institution National Medical Surgical Center named after N. I. Pirogov of the Ministry of health of the Russian Federation

Moscow, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Vladislav Sarzhevskiy, MD, PhD

Role: CONTACT

+74956037217

Nikita Mochkin, MD, PhD

Role: CONTACT

+74956037217

Facility Contacts

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Vladislav Sarzhevskiy, MD, PhD

Role: primary

+74956037217

Nikita Mochkin, MD, PhD

Role: backup

+74956037217

References

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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.

Reference Type BACKGROUND
PMID: 23550793 (View on PubMed)

Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Muller 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. doi: 10.1016/S0140-6736(02)08938-9.

Reference Type BACKGROUND
PMID: 12086759 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9808548 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25687795 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18182663 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22861163 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23248254 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21816830 (View on PubMed)

Other Identifiers

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BeEAC-1

Identifier Type: -

Identifier Source: org_study_id

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