Clinical trial NCT03527628: OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Classical Hodgkin Lymphoma
Hodgkin Lymphoma (Category)
Hodgkin Disease
Hodgkin Lymphoma
Keywords: Stage II B Classical Hodgkin Lymphoma
Stage III Classical Hodgkin Lymphoma
Stage IV Classical Hodgkin Lymphoma
Lead sponsor: King Abdullah International Medical Research Center
Sponsor class: OTHER
First posted: 2018-05-17
Enrollment: 220
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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Detailed description: With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative.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

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).

Primary outcomes:
measure: ]Progression Free Survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 5 years
Other outcomes:
measure: Reduction of lung toxicity
timeFrame: 6 months
measure: Overall toxicity
timeFrame: 6 months
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Abdulaziz Medical City, Ministry of National Guard
Study officials:
affiliation: King Abdulaziz Medical City, Ministry of National Gaurd (KAMC)
name: Ayman Hejazi, MD
role: PRINCIPAL_INVESTIGATOR
References: