OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy

Phase 2

• Conditions: Classical Hodgkin Lymphoma; Hodgkin Disease; Hodgkin Lymphoma; Hodgkin Lymphoma (Category)
• Interventions: Drug: Adriamycin; Drug: Cyclophosphamide; Drug: Vinblastine; Drug: Dacarbazine; Drug: ABVD; Drug: Brentuximab Vedotin

• Registration Number: NCT03527628
• Lead Sponsor: King Abdullah International Medical Research Center

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With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative.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

Study Timeline

• Study First Submitted: 2017-12-12
• Study Start: 2018-01-01
• Study First Submitted QC: 2018-05-16
• Study First Posted: 2018-05-17
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-14
• Last Update Posted: 2019-11-18
• Primary Completion: 2021-01-15
• Study Completion: 2022-01-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 220

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with PET-2 Negative Result	Cyclophosphamide	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)
Patients with PET-2 Negative Result	Vinblastine	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)
Patients with PET-2 Negative Result	ABVD	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)
Patients with PET-2 Positive Result	Brentuximab Vedotin	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
Patients with PET-2 Negative Result	Adriamycin	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)
Patients with PET-2 Positive Result	ABVD	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
Patients with PET-2 Positive Result	Cyclophosphamide	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
Patients with PET-2 Positive Result	Dacarbazine	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
Patients with PET-2 Negative Result	Dacarbazine	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)
Patients with PET-2 Positive Result	Adriamycin	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
Patients with PET-2 Positive Result	Vinblastine	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

Primary Outcome Measures

Name	Time	Method
]Progression Free Survival (PFS)	3 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	5 years	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.

Trial Locations

Locations (1)

King Abdulaziz Medical City, Ministry of National Guard; 🇸🇦 Riyadh, Saudi Arabia