Lowdose Nivolumab in Combination With AVD as Front Line Therapy for Classic Hodgkin's Lymphoma

Safety and Efficacy Evaluation of Low-dose Nivolumab in Combination With AVD as Frontline Therapy for Classic Hodgkin's Lymphoma

This study aims to prove the efficacy and safety of low dose nivolumab (40mg as the lowest available presentation) in combination with AVD (adriamycin,vinblastine sulfate and dacarbazine) as frontline treatment for classic Hodgkin's lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Safety Issues; Efficacy, Self
• Intervention / Treatment: Drug: low dose nivolumab in combination with AVD

Detailed Description

The main objective of this project is to prove the efficacy and safety of Nivolumab used as an standard dose of 40mg ( as the lowest available presentation) in combination with AVD as frontline therapy for Hodgkin's lymphoma.

Patients classification.

We will categorize patients in three groups as follows:

1. Early stages by Ann-arbor classification (I,II) with no risk factors (as stablished by NCCN's guidelines criteria).
2. Early stages by Ann.arbor classification (I,II) with risk factors ( as stablished by NCCN's guidelines criteria).
3. Advanced stages by Ann-arbor classification (III,IV).

Methodology:

• Patients will receive two initial cycles of NAVD therapy ( each with two applications in day 1 and 15) and then will be evaluated with an interim PET/CT after completing cycle 2.
• According to the PET C/T results, patients will be categorized as fast responsers (patients who achieve Deauville 1-3 classification) and low responsers ( patients who achieve Deauville 4-5).
• Fast responsers will receive following cycles without nivolumab (2 extra cycles for patients categorized as early stage with no risk factors, 4 extra cycles for patients categorized as early stages with risk factors and for advanced stages).
• Patients will receive medical evaluation at first meeting, during their treatment and after conclusion of the treatment with physical examination and laboratory tests according to medical criteria.
• Adverse effects will be recorded and managed following the guidelines for immunotherapy and chemotherapy indications.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Gomez Almaguer, MD; Phone Number: +52 8183486136; Email: dgomezalmaguer@gmail.com

Study Locations

• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Recruiting
      • Hospital Universitario Dr Jose Eleuterio Gonzalez
      • Contact: Perla R Colunga Pedraza, MD; Phone Number: +52 8183486136; Email: colunga.perla@gmail.com
      • Contact: Antonio Vega Mateos, MD; Phone Number: +52 8183488510; Email: antoniovegamat@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with recent diagnosis of classic Hodgkin's lymphoma demonstrated by incisional or excisional biopsy of adenopathy.
• Treatment naive patients.
• Any stage
• Any functional status.

Exclusion Criteria:

• Patients with refractory or relapsed disease.
• Patients with non classical variety.
• Patients with chronic or active infections at the moment of recruiting.
• Patients younger than 16 years old.
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LowN-AVD; classic Hodgkin's lymphoma patients receiving low dose nivolumab in combination with AVD	Drug: low dose nivolumab in combination with AVD; Nivolumab as an standard dose of 40mg in combination with AVD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine general response	To determine patients achieving either a complete response or a partial response as demonstrated with PET C/T evaluation.	Six weeks after completion of therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response duration	To evaluate the duration of the response achieved with the therapy.	up to 2 years
Adverse effects	To record the side effects associated with the treatment as stablished by the international guidelines for chemotherapy and immunotherapy.	through the study completion and up to 6 months

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez
• Investigators: Principal Investigator: Perla R Colunga Pedraza, MD, Hospital Universitario Jose Eleuterio Gonzalez

Publications and helpful links

General Publications

• Hwang YY, Khong PL, Kwong YL. Low-dose nivolumab induced remission in refractory classical Hodgkin lymphoma. Ann Hematol. 2017 Jul;96(7):1219-1220. doi: 10.1007/s00277-017-3007-9. Epub 2017 Apr 22. No abstract available.
• Lepik KV, Fedorova LV, Kondakova EV, Zalyalov YR, Babenko EV, Lepik EE, Kotselyabina PV, Beynarovich AV, Popova MO, Volkov NP, Stelmakh LV, Baykov VV, Moiseev IS, Mikhailova NB, Kulagin AD, Afanasyev BV. A Phase 2 Study of Nivolumab Using a Fixed Dose of 40 mg (Nivo40) in Patients With Relapsed/Refractory Hodgkin Lymphoma. Hemasphere. 2020 Sep 23;4(5):e480. doi: 10.1097/HS9.0000000000000480. eCollection 2020 Oct.
• Brockelmann PJ, Goergen H, Keller U, Meissner J, Ordemann R, Halbsguth TV, Sasse S, Sokler M, Kerkhoff A, Mathas S, Huttmann A, Bormann M, Zimmermann A, Mettler J, Fuchs M, von Tresckow B, Baues C, Rosenwald A, Klapper W, Kobe C, Borchmann P, Engert A. Efficacy of Nivolumab and AVD in Early-Stage Unfavorable Classic Hodgkin Lymphoma: The Randomized Phase 2 German Hodgkin Study Group NIVAHL Trial. JAMA Oncol. 2020 Jun 1;6(6):872-880. doi: 10.1001/jamaoncol.2020.0750.
• Chan TSY, Hwang YY, Khong PL, Leung AYH, Chim CS, Tse EWC, Kwong YL. Low-dose pembrolizumab and nivolumab were efficacious and safe in relapsed and refractory classical Hodgkin lymphoma: Experience in a resource-constrained setting. Hematol Oncol. 2020 Dec;38(5):726-736. doi: 10.1002/hon.2787. Epub 2020 Aug 20.
• Ramchandren R, Domingo-Domenech E, Rueda A, Trneny M, Feldman TA, Lee HJ, Provencio M, Sillaber C, Cohen JB, Savage KJ, Willenbacher W, Ligon AH, Ouyang J, Redd R, Rodig SJ, Shipp MA, Sacchi M, Sumbul A, Armand P, Ansell SM. Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. J Clin Oncol. 2019 Aug 10;37(23):1997-2007. doi: 10.1200/JCO.19.00315. Epub 2019 May 21.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 6, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; hodgkin's lymphoma; lowdose nivolumab; NAVD
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: HE23-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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