OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy ((Optimist))

King Abdullah International Medical Research Center

Status and phase: Unknown; Phase 2

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

Treatments: Drug: Cyclophosphamide; Drug: Brentuximab Vedotin; Drug: Dacarbazine; Drug: Adriamycin; Drug: Vinblastine; Drug: ABVD

Study type: Interventional

Funder types: Other

Identifiers

NCT03527628

RC-16/150

Details and patient eligibility

About

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.

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With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative.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

Enrollment: 220 estimated patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 2 patient groups

Patients with PET-2 Negative Result

Other group

Description:

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)

Treatment:

Drug: ABVD

Drug: Vinblastine

Drug: Dacarbazine

Drug: Adriamycin

Drug: Cyclophosphamide

Patients with PET-2 Positive Result

Other group

Description:

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

Treatment:

Drug: ABVD

Drug: Vinblastine

Drug: Dacarbazine

Drug: Adriamycin

Drug: Brentuximab Vedotin

Drug: Cyclophosphamide