OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy

Hodgkin Lymphoma Clinical Trial

— (Optimist)  

Official title:

A Phase II, Multicenter, Open Label Study of Treatment Intensification With ACVD and Brentuximab-Vedotin in Advanced-stage Hodgkin Lymphoma Patients With a Positive Interim PET Scan After 2 ABVD Cycles

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03527628
• Other study ID #: RC-16/150
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2018
• Est. completion date: January 15, 2022

Study information

• Verified date: November 2019
• Source: King Abdullah International Medical Research Center
• Contact: Ayman Alhejazi, MD
• Phone: 801 1111
• Email: hejazia[@]ngha.med.sa
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative.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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: January 15, 2022
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease
• Hodgkin Lymphoma
• Hodgkin Lymphoma (Category)
• Lymphoma

Intervention

Drug:
• Adriamycin
25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.
• Cyclophosphamide
400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle
• Vinblastine
6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle
• Dacarbazine
375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle
• Brentuximab Vedotin
1.2mg/kg Intravenous infusion, in days 1 and 15 of each 28 day cycle
• ABVD
All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)

Locations

Country	Name	City	State
Saudi Arabia	King Abdulaziz Medical City, Ministry of National Guard	Riyadh

Sponsors (1)

Lead Sponsor	Collaborator
King Abdullah International Medical Research Center

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Reduction of lung toxicity	The ability of ACVD to reduce lung toxicity as compared to ABVD by performing a pulmonary function test (PFT) at baseline and end of treatment	6 months
Other	Overall toxicity	The feasibility of the entire program in terms of grade 3 or 4 NCICTCAE or WHO toxicity	6 months
Primary	]Progression Free Survival (PFS)	PFS is estimated from the date of diagnosis until the date of first disease progression or relapse, death for any cause.; Superior overall 3 year progression-free survival of patients with PET 2 positive after 2 cycles of ABVD with ACVD and BV compared to historical control of ABVD treated patients and PET 2 negative patients with ACVD only after 2 cycles of ABVD.	3 years
Secondary	Overall Survival (OS)	Superior overall survival of PET 2 positive patients treated with ACVD + BV after 2 cycles of ABVD and PET 2 negative treated with ACVD after 2 cycles of ABVD. It is estimated from the date of diagnosis up to study completion or death, whichever came first, assessed up to 5 years.	5 years