OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy

NCT ID: NCT03527628

Last Updated: 2019-11-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2022-01-15

Brief Summary

This is a prospective, multi-center, open-label, phase II clinical trial, aims to assess the effectiveness of the combination ACVD (Adriamycin, Cyclophosphamide, Vinblastine and Dacarbazine) and BV (Brentuximab Vedotin) in PET-2 positive advanced-stage HL patients, in order to improve the overall long-term disease control in the entire cohort of advanced-stage HL.

Detailed Description

With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative. All advanced stage HL patients will receive 2 cycles of the standard treatment ABVD and assessed with PET-2 scan.

Knowing that Cyclophosphamide toxicities include cytopenias, amenorrhea and male infertility. These toxicities are mainly dependent on the total cumulative dose. Doses less than 4 g/m2 are not associated with sterility or major toxicity, doses higher than this can lead to azoospermia which was reversible in many cases therefore the cumulative dose will be used in this study is 3200 mg. Additionally, Brentuximab Vedotin has shown significant activity in relapsed refractory HL with minor toxicities.

PET scan after 2 cycles of ABVD has proven to be an excellent tool to identify patients that will have long term PFS of 95% when it is negative and only progression-free survival (PFS) of less than 15% when it is positive.

The primary endpoint of the study will be to assess the overall 3-Y PFS of the entire cohort of patients.

Conditions

Classical Hodgkin Lymphoma; Hodgkin Lymphoma (Category); Hodgkin Disease; Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with PET-2 Negative Result

After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results

PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)

Group Type: OTHER

Adriamycin

Intervention Type: DRUG

25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.

Cyclophosphamide

Intervention Type: DRUG

400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle

Vinblastine

Intervention Type: DRUG

6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle

Dacarbazine

Intervention Type: DRUG

375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle

ABVD

Intervention Type: DRUG

All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)

Patients with PET-2 Positive Result

After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results

PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin

Group Type: OTHER

Adriamycin

Intervention Type: DRUG

25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.

Cyclophosphamide

Intervention Type: DRUG

400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle

Vinblastine

Intervention Type: DRUG

6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle

Dacarbazine

Intervention Type: DRUG

375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle

Brentuximab Vedotin

Intervention Type: DRUG

1.2mg/kg Intravenous infusion, in days 1 and 15 of each 28 day cycle

ABVD

Intervention Type: DRUG

All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)

Interventions

Adriamycin

25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.

Intervention Type: DRUG

Cyclophosphamide

400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle

Intervention Type: DRUG

Vinblastine

6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle

Intervention Type: DRUG

Dacarbazine

375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle

Intervention Type: DRUG

Brentuximab Vedotin

1.2mg/kg Intravenous infusion, in days 1 and 15 of each 28 day cycle

Intervention Type: DRUG

ABVD

All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)

Intervention Type: DRUG

Other Intervention Names

Doxorubicin; Cytoxan®; Neosar®; Cycloblastin; Revimmune; Velbe ®; DTIC; ADCETRIS®; SGN-35; (Adriamycin, Bleomycin, Vinblastine and Dacarbazine )

Eligibility Criteria

Inclusion Criteria

• All the following parameters should be met

• Newly diagnosed untreated ,histologically proven CD30 positive classical Hodgkin Lymphoma (cHL)
• Advanced stage (Stage IIB to IVB) as defined by Ann Arbor Staging System (Appendix 1)
• Age ≥ 14, < 60 years
• ECOG performance status 0-2
• Written informed consent for the trial
• Adequate contraceptive precautions for all patients of childbearing potential
• All prognostic group

Exclusion Criteria

• Any of the following:

• Pregnant or lactating women.
• Presence of the following:

1. Heart failure with LVEF <50%

2. Liver enzymes, >2 ULN not attributed to Hodgkin Lymphoma.

3. Another malignancy that is currently clinically significant or requires active intervention

• Early-stage disease (Stage I- IIA).
• Patients who are already participating to another clinical trial.
• Known history of HIV seropositive status
• ECOG performance status 3-4
• Creatinin clearance <50 ml/min
• Prior treatment for Hodgkin Lymphoma excluding steroids
• Medical or psychiatric conditions compromising the patient's ability to give informed consent
• Patients with serious active infection
• Pre-existing peripheral neuropathy (grade 2 or more).

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Abdullah International Medical Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ayman Hejazi, MD

Role: PRINCIPAL_INVESTIGATOR

King Abdulaziz Medical City, Ministry of National Gaurd (KAMC)

Locations

King Abdulaziz Medical City, Ministry of National Guard

Riyadh, , Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Ayman Alhejazi, MD

Role: CONTACT

hejazia@ngha.med.sa

801 1111 ext. 53388

Facility Contacts

Ayman Hejazi, MD

Role: primary

hejazia@ngha.med.sa

+966 8011111 ext. 53388

Other Identifiers

RC-16/150

Identifier Type: -

Identifier Source: org_study_id