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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hodgkin Disease; Hodgkin Lymphoma; Classical Hodgkin Lymphoma; Hodgkin Lymphoma (Category)
• Intervention / Treatment: Drug: Adriamycin; Drug: Cyclophosphamide; Drug: Vinblastine; Drug: Dacarbazine; Drug: ABVD; Drug: Brentuximab Vedotin

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With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative.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 Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ayman Alhejazi, MD; Phone Number: 53388 801 1111; Email: hejazia@ngha.med.sa

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 22390
    • Recruiting
    • King Abdulaziz Medical City, Ministry of National Guard
    • Contact: Ayman Hejazi, MD; Phone Number: 53388 +966 8011111; Email: hejazia@ngha.med.sa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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)	Drug: Adriamycin; 25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.; Other Names: Doxorubicin; Drug: Cyclophosphamide; 400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle; Other Names: Cycloblastin; Revimmune; Cytoxan®; Neosar®; 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; Other Names: Velbe ®; Drug: Dacarbazine; 375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle; Other Names: DTIC; Drug: ABVD; All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2); Other Names: (Adriamycin, Bleomycin, Vinblastine and Dacarbazine )
Other: 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	Drug: Adriamycin; 25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.; Other Names: Doxorubicin; Drug: Cyclophosphamide; 400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle; Other Names: Cycloblastin; Revimmune; Cytoxan®; Neosar®; 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; Other Names: Velbe ®; Drug: Dacarbazine; 375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle; Other Names: DTIC; Drug: ABVD; All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2); Other Names: (Adriamycin, Bleomycin, Vinblastine and Dacarbazine ); Drug: Brentuximab Vedotin; 1.2mg/kg Intravenous infusion, in days 1 and 15 of each 28 day cycle; Other Names: SGN-35; ADCETRIS®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
]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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Overall toxicity	The feasibility of the entire program in terms of grade 3 or 4 NCICTCAE or WHO toxicity	6 months

Collaborators and Investigators

• Sponsor: King Abdullah International Medical Research Center
• Investigators: Principal Investigator: Ayman Hejazi, MD, King Abdulaziz Medical City, Ministry of National Gaurd (KAMC)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): January 15, 2021
• Study Completion (Anticipated): January 15, 2022

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Stage II B Classical Hodgkin Lymphoma; Stage III Classical Hodgkin Lymphoma; Stage IV Classical Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Dacarbazine; Bleomycin; Brentuximab Vedotin; Vinblastine
• Other Study ID Numbers: RC-16/150

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No