The Efficacy of Bendamustine, Gemcytabine, Dexamethasone Salvage Chemotherapy With Autologous Stem Cell Transplantation (BURGUND) Consolidation in Advanced Classical Hodgkin Lymphoma Patients Not Responding to ABVD Therapy

Study Overview
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Brief Summary
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The objective of the study is evaluation of efficacy of Bendamustine, Gemcytabine, Dexamethasone (BGD) salvage therapy with autologus stem cell transplantation (ASCT) consolidation in advanced classical Hodgkin lymphoma patients not responding to ABVD therapy.

Detailed Description
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Treatment regimen: Bendamustine (B) 90 mg/m2 iv day 1, 2 Gemcytabine (G) 800 mg/m2 iv day 1, 4 Dexamethasone (D) 40 mg iv/po day 1,2,3,4 Course of treatment every 21-28 days, 4 courses of treatment max; next round of treatment may be given if ANC>1000/μl and PLT>75000/μl. Up to 7-day delay is permitted.

Official Title
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The Efficacy of Bendamustine, Gemcytabine, Dexamethasone (BGD) Salvage Chemotherapy With Autologous Stem Cell Transplantation (ASCT) Consolidation in Advanced Classical Hodgkin Lymphoma Patients Not Responding to ABVD Therapy- Multicentre Phase II Clinical Study (PLRG-HL1/BURGUND)

Conditions
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Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Bendamustine
* Drug: Gemcitabine
* Drug: Dexamethasone
* Diagnostic Test: PET/CT
* Procedure: Autologous Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Classical Hodgkin's Lymphoma treated with ABVD regimen with PET scan/CT performed before, during and after treatment, and also one of the following: positive result (Deauville 4 and 5) of early PET scan after 2 ABVD courses disease progression or relapse after first-line ABVD treatment or ABVD and radiotherapy combination treatment No contraindications for salvage chemotherapy and ASCT At least one measurable malignancy ECOG performance status ≤ 3 Written signed and dated informed consent prior to any study procedures being performed Exclusion Criteria: Non-Classical Hodgkin's Lymphoma Other than ABVD first-line treatment, preceding patient's inclusion Lack of PET scans performed in accordance with inclusin criteria during ABVD treatment Transformation of Hodgkin's Lymphoma Central Nervous System (CNS) Metastases Contraindications for ASCT or lack of patient's consens for the procedure Second malignancy - active or cured less than 5 years prior Uncontrolled diabetes Hepatic impairment (bilirubin concentration ≥ 1.5 x ULN, SGOT > 5 x ULN), if non-realted to the lymphoma or Gilbert's syndrome HIV infection Active HBV or HCV infection. Subjects who have had Hepatitis B and are abHBC positive, need to undergo HBV DNA test using a Polymerase Chain Reaction (PCR) technique and be applied appropriate preventive treatment. Pregnancy or lactation Hypersensitivity to any of the drugs Lack of written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGD therapy<br>Bendamustine, Gemcitabine, Dexamethasone | Drug: Bendamustine<br>* Bendamustine (B) 90 mg/m2 i.v. day 1, 2<br>* Other names: Treanda;Drug: Gemcitabine<br>* Gemcitabine (G) 800 mg/m2 i.v. day 1, 4<br>* Other names: Gemzar;Drug: Dexamethasone<br>* Dexamethasone (D) 40 mg i.v./p.o. day 1,2,3,4<br>Diagnostic Test: PET/CT<br>* PET scan/CT must be performed after first 2 courses of BGD treatment. Results evaluation: in case of a CMR/CR or PMR/PR, ASCT must be performed within 3 months after the end of BGD treatment in case of SMD - exclusion from the trial in case of PMD - exclusion from the trial<br>Procedure: Autologous Stem Cell Transplant<br>* Must be performed within 3 months after the end of BGD treatment. When it is not possible to perform ASCT, despite CMR or PMR response, within 3 months after second course of BGD treatment, it is permissible to extend the therapy up to 4 cycles. PET scan/CT must be repeated before performing ASCT.<br>* Other names: ASCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (overall response rate) | CR (complete response) + PR (partial response) | Evaluated at the end of Cycle 2 of BGD (every cycle is 21-28 days) | 
| PFS (progression-free survival) | Staying free of disease progression. | Time measured from date of of Cycle 2 of BGD treatment (every cycle is 21-28 days) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS (overall survival) | The length of time from the start of treatment, that patients diagnosed with the disease are still alive. | Time measured from Day 1 of Cycle 1 of BGD treatment (every cycle is 21-28 days) until the date of death from any cause, assessed up to 24 months (measured for patients that have undergone ASCT after BGD tratment). | 
| OMRR (overall metabolic response rate) | OMRR= CMR (complete metabolic response) + PMR (partial metabolic response) | Evaluated a the end of Cycle 2 of BGD treatment (every cycle is 21-28 days) and after ASCT (up to 150 days after Day 1 of Cycle 1 of BGD treatment). | 
| BGD tolerability assessment. | Number of participants with treatment-related adverse events and serious adverse events. | 24 months from the start of BGD treatment | 
| MR (mobilization rate) | Evaluation of stem cells mobilization efficacy in patients on BGD regimen. | Evaluated after the end of Cycle 2 of BGD (every cycle is 21-28 days), before tranplantation (up to Day 150 of treatment). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Immunochemotherapy, Salvage therapy, Bendamustine, Gemcitabine, Dexamethasone, Hodgkin's Lymphoma, ASCT