First Line Chemotherapy for Classical Hodgkin Lymphoma in Russia (HL-Russia-1)

Hodgkin Lymphoma, Adult Clinical Trial

— HL-Russia-1  

Official title:

First Line Chemotherapy for Classical Hodgkin Lymphoma in Russia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04638790
• Other study ID #: HL-Russia-1
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2022
• Source: State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia
• Contact: Vladislav Sarzhevskiy, PhD
• Phone: +79104360040
• Email: vladsar100[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The HL-Russia-1 is a non-randomized, open-label, multicenter, phase III, 3-arm study. The primary objective is to assess efficacy, safety and progression-free survival (PFS) of different approaches (earle favorable, early unfavorable and advanced stages) to first line chemotherapy for classical Hodgkin Lymphoma (HL).

Description:

The study is devoted to patients affected with Hodgkin Lymphoma in Russia.

The study aims to assess the efficacy and safety of three different approaches to first line chemotherapy for classical Hodgkin Lymphoma (HL):

1. Early favourable (stages I-IIA without unfavorable risk factors). Patients will receive two courses of standard ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). Those with a PET-2 (positron emission tomography) negative scan (Deauville Score 1-3) will proceed with radiotherapy on initially involved site (20 Gy). Those with a PET-2 Deauville score 4 will proceed with additional 2 ABVD courses. After that, those with a PET-4 negative scan (Deauville Score 1-3) will proceed with radiotherapy on initially involved site (30 Gy). In case of PET-4 positive scan after 4 ABVD cycles (Deauville score 4-5) patients will be planned to perform the biopsy and in case of positive results, proceed to high-dose chemotherapy with autologous stem cell transplantation (HDT with ASCT). In case of negative results of the biopsy, they will proceed with additional 2 ABVD courses and restage again. Those with a PET-6 negative scan (Deauville Score 1-3) will proceed with radiotherapy on initially involved site (30 Gy). In case of PET-6 positive scan (Deauville score 4-5) patients will be proceeded to HDT with ASCT.

Those with a PET-2 Deauville score 5 after 2 ABVD courses will be planned to perform the biopsy and in case of positive results, proceed to HDT with ASCT. In case of negative results of the biopsy they will proceed with additional 2 ABVD courses and restage again. Those with a PET-4 negative scan (Deauville Score 1-3) will proceed with radiotherapy on initially involved site (30 Gy). In case of PET-4 positive scan (Deauville score 4-5) patients will be proceeded to HDT with ASCT.

2. Early unfavorable (stages IA-B, IIA bulky and/or extranodal lesions, patients younger 50 years). Patients will receive two courses of EACODD-14 (etoposide 100 mg/m2 days 1-3, doxorubicin 50 mg/m2 day 1, cyclophosphamide 650 mg/m2 day 1, vincristine 1,4 mg/m2 day 8, dacarbazine 375 mg/m2 day 1, dexamethasone 20 mg days 1-3; cycle is repeated every 14 days). Those with a PET-2 negative scan (Deauville Score 1-3) will be deescalated to 2 courses of AVD (Adriamycin, vinblastine, and dacarbazine) and consolidative radiotherapy on initially involved site (30 Gy). Those with a PET-2-positive scan (Deauville score 4-5) will proceed with additional 2 EACODD-14 courses. After that, those with a PET-4 negative scan (Deauville Score 1-3) will proceed with radiotherapy on initially involved site (30 Gy). In case of PET-4 positive scan after 4 EACODD-14 cycles (Deauville score 4-5) patients will proceed with additional 2 EACODD-14 courses. After that, those with a PET-6 negative scan (Deauville Score 1-3) will proceed with radiotherapy on initially involved site (30 Gy). In case of PET-6 positive scan (Deauville score 4-5) patients will be proceeded to HDT with ASCT.

3. Advanced stages (younger 50 years). Patients will receive two courses of EACODD-14. Those with a PET-2 negative scan (Deauville Score 1-3) will proceed with 4 additional courses of EACODD-14. After that, patients with residual tumor ˂ 4 cm, will stop the therapy and start the follow-up phase. Patients with residual tumor ≥ 4 cm, will undergo consolidative radiotherapy on residual tumor (30 Gy). Those with a PET-2-positive scan (Deauville score 4-5) will proceed with additional 4 additional courses of EACODD-14. After that, those with a PET-6 negative scan (Deauville Score 1-3) will proceed with radiotherapy on residual tumor ≥ 2,5 cm (30 Gy). In case of PET-6 positive scan (Deauville score 4-5) patients will be proceeded to HDT with ASCT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed classical HL

• Previously untreated disease

• Age 18-5 years

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =2

• Adequate organ and marrow function as defined below: absolute neutrophil count >1,0 x109/L, platelets >75 x109/L

• Total bilirubin <2 mg/dl without a pattern consistent with Gilbert's syndrome

• Creatinine within normal institutional limits or creatinine clearance >50 mL/min/1.73 m2

• Females of childbearing must have a negative pregnancy test at medical supervision even if had been using effective contraception

• Life expectancy > 6 months

• Able to adhere to the study visit schedule and other protocol requirements

• Sign (or their legally acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

• Access to PET-CT (positron emission computed tomography) scans facilities

Exclusion Criteria:

• Nodular Lymphocyte Predominant HL

• Prior chemotherapy or radiation therapy

• Pregnant or lactating females

• Cardiac arrhythmia, conduction abnormalities, ischemic cardiopathy, left ventricular hypertrophy or left ventricular ejection fraction (LVEF) =50% at echocardiography.

• Abnormal QTc (corrected QT interval) interval prolonged (>450 msec in males; >470 msec in women)

• Uncontrolled infectious disease

• Human immunodeficiency virus (HIV) positivity or active infectious A, B or C hepatitis. HBsAg-negative patients with anti-HBc (hepatitis B core antigen) antibody and can be enrolled provided that Hepatitis B Virus (HBV)-DNA are negative and that antiviral treatment with nucleos(t)ide analogs is provided

• Uncompensated diabetes

• Refusal of adequate contraception

• Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment.

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma, Adult
• Lymphoma

Intervention

Drug:
• Doxorubicin
25 mg/m2 i.v. day 1,15 for ABVD/AVD
• Bleomycin
10,000 units/m2 i.v. days 1,15 for ABVD
• Vinblastine
6 mg/m2 i.v. days 1,15 for ABVD/AVD
• Dacarbazine
375 mg/m2 i.v. days 1,15 for ABVD/AVD
• Etoposide
100 mg/m2 i.v. days 1-3
• Doxorubicin
50 mg/m2 i.v. day 1 for EACODD-14
• Cyclophosphamide
650 mg/m2 i.v. day 1
• Vincristine
1,4 mg/m2 i.v. day 8
• Dexamethasone
20 mg i.v. days 1-3
• Dacarbazine
375 mg/m2 i.v. day 1 for EACODD-14

Locations

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

Sponsors (1)

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

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate (CR)	CR rate is defined as the proportion of patients achieving a CR after 3 months of chemotherapy (interim) and at the end of treatment	up to 6 months
Primary	Acute Toxicity	The severity of the toxicities will be classified according to definitions of Common Terminology Criteria for Adverse Event (CTCAE) version 4.3. It will be determined by the incidence of severe, life- threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events (Infusion-related reactions)	6 months
Primary	Late Toxicity	The severity of the toxicities will be classified according to definitions of Common Terminology Criteria for Adverse Event (CTCAE) version 4.3. It will be determined by the incidence of severe, life- threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events (Infusion-related reactions)	5 years
Primary	Event-Free Survival (EFS)	EFS will be measured from the time from entry onto a study to any treatment failure including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of new treatment lacking documented progression, or death)	5 years
Primary	Disease free survival (DFS)	DFS will be measured from the time of occurrence of disease-free state or attainment of a CR to disease recurrence or death as a result of lymphoma or acute toxicity of treatment	5 years
Secondary	Overall survival (OS)	OS is defined as the time from entry onto the clinical trial until death as a result of any cause	5 years