Clinical Trials

Study Overview

This study is looking at the benefits of adding immunotherapy to the usual treatment for early-stage classical Hodgkin lymphoma (stages I and II). The usual treatment includes chemotherapy, and sometimes radiation. Adding immunotherapy to standard treatment might improve survival chances and could result in fewer side effects, both short and long term, for people with this type of lymphoma.

This study aims to find out if this combined approach is more effective than the standard treatment alone.

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Trial identification number

NCI-2022-10845

The medicine(s) being studied.

Immunotherapy: The added treatments are two types of immunotherapy: brentuximab vedotin and nivolumab. Brentuximab vedotin combines an antibody that targets cancer cells with a drug that kills them. Nivolumab helps your immune system fight the cancer more effectively. Both of these medicines are already available for use in patients with cancer.
Chemotherapy: The standard chemotherapy drugs used in this trial include doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, procarbazine hydrochloride, cyclophosphamide, etoposide, vincristine, and prednisone. These drugs work in different ways to stop cancer cells from growing and dividing, which helps kill them or stop them from spreading.
Radiation Therapy: For some patients, high-energy x-rays may be used to kill tumor cells and shrink tumors.

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How does the new medicine work (Mechanism of Action)?

Brentuximab is part of a unique class of therapy known as antibody drug conjugates designed to target cells expressing CD30.

CD30 is a member of the tumor necrosis factor receptor family and is expressed on the surface of certain peripheral T-cell lymphomas (PTCL), such as systemic anaplastic large cell lymphoma (sALCL) cells, and on Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL)
Detection of CD30 can help identify patients who may be appropriate candidates for CD30-directed therapy

Nivolumab is a type of medication known as an immune checkpoint inhibitor. It works by targeting a protein on immune cells called PD-1 (programmed death-1). Normally, PD-1 acts as a type of "off switch" that helps keep the body’s immune responses in check by preventing the activation of T-cells, which could otherwise attack normal cells in the body.

Cancer cells can take advantage of this pathway by expressing PD-L1, a ligand for PD-1, thereby protecting themselves from being attacked by the immune system. Nivolumab blocks PD-1, disrupting this pathway and enabling the immune system, specifically T-cells, to attack cancer cells more effectively.

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What will be evaluated (Key endpoints)?

Rapid Early Responders to standard chemotherapy: Add on immunotherapy

Objective: Assess if immunotherapy (brentuximab vedotin and nivolumab) is more effective (than continuing standard chemotherapy for patients who show a quick, positive response to initial treatment.‍
Approach: After the first two cycles of standard chemotherapy (ABVD - doxorubicin, bleomycin, vinblastine, dacarbazine), patients who quickly show improvement on their PET scans will switch to immunotherapy to see if this enhances their progression-free survival (PFS), meaning the cancer does not worsen.

Slow Early Responders to standard chemotherapy: Add on immunotherapy + radiotherapy

Objective: Evaluate if adding immunotherapy and involved site radiation therapy (ISRT) to the treatment regimen provides better outcomes (progressional free survival or PFS) than standard chemotherapy alone for patients who show a slower initial response.
Approach: Patients showing a slower response on early PET scans after two cycles of ABVD will either continue with standard chemotherapy or receive a combination of immunotherapy and radiation. The goal is to compare the effectiveness in preventing cancer progression.

These strategies aim to customize treatment based on how quickly patients respond to initial chemotherapy, optimizing the chance for better long-term outcomes.

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Who may participate (Inclusion criteria)?

Age Range:
- Participants must be between 5 and 60 years old at the time of enrollment.
Disease Confirmation and Stage:
- You must be newly diagnosed with early stage (I or II) classic Hodgkin lymphoma. This includes various subtypes like nodular sclerosis or mixed cellularity.
- There needs to be at least one measurable area of the disease, with a lesion size of 1.5 cm in diameter or larger.
Diagnostic Tests:
- A PET scan (using CT or MRI) must have been completed within 42 days before joining the study. If a PET-MRI is used, an additional CT scan with contrast is required.
- Chest X-rays are needed for assessment. Children (5-17 years) require an upright chest X-ray. Adults can have either a chest X-ray or a CT scan of the chest.
Health and Performance Status:
- Adults (18 years and older) must have a Zubrod performance score of 0, 1, or 2, indicating how the disease affects their daily living abilities.
- Children (under 18 years) should have a Lansky performance score of 50 or above, showing a moderate level of activity.
Kidney Function:
- Specific creatinine levels are required depending on age and gender to ensure good kidney function.
- Adults need a creatinine clearance of at least 30 mL/min, which shows how well the kidneys filter waste.
- Tests for GFR (a measure of kidney function) using certain methods are necessary, not just estimates.
Liver and Heart Function:
- Total bilirubin levels must be no more than twice the normal limit unless it’s due to specific conditions.
- Liver enzymes (AST and ALT) should be within three times the normal range unless there are extenuating circumstances.
- Heart function should be confirmed as adequate through various scans, ensuring at least a 27% shortening fraction or 50% ejection fraction.
Lung Function:
- Lung capacity should be at least 50% of the expected value for someone your age and health condition, checked by a lung function test or, if that’s not possible, an oxygen saturation of more than 92% on room air.
Other Conditions:
- Patients with HIV must be on effective therapy with an undetectable viral load.
- Those with hepatitis B or C must have controlled or resolved infections.
This study aims to ensure participants are in a condition that allows them to safely receive and potentially benefit from the treatment while providing accurate data on the effectiveness of the therapies being tested.‍

Who may not participate (Exclusion criteria)?

Specific Hodgkin Lymphoma Type: If you have nodular lymphocyte predominant Hodgkin lymphoma, you are not eligible.
Lung Issues: Anyone with active lung diseases like interstitial pneumonitis or lung disease.
Immune System Conditions: Those with inherited or acquired immune deficiencies that aren’t well-controlled, or if you're taking medication for these conditions.
Serious Health Issues: If you have uncontrolled illnesses that could affect safety, such as certain infections, heart conditions, or severe digestive problems.
Recent Use of Immunosuppressants: You shouldn't have taken high doses of steroids or other immune-weakening medicines within 14 days before joining. Low doses for hormone replacement or topical steroids are okay unless you have active autoimmune disease.
Neurological Conditions: If you have significant nerve damage or Charcot-Marie-Tooth syndrome.
Other Cancers or Treatments: If you have another type of cancer or have had treatments like chemotherapy, radiation, or antibody treatments for Hodgkin lymphoma, or any organ or stem cell transplant.
Vaccinations: You shouldn't have received live vaccines within 30 days before starting the study. mRNA vaccines like COVID-19 vaccines are allowed.

Requirements for Women and Family Planning:

Pregnancy: Women must not be pregnant and must have a pregnancy test done before joining because the study drugs could harm the fetus.
Breastfeeding: If you are breastfeeding or plan to start, you are not eligible.
Contraception: If you are sexually active and can have children, you must agree to use effective birth control during and for several months after the treatment to avoid pregnancy.

Consent and Regulations:

Informed Consent: You and/or your guardians must understand and sign an informed consent form.
Regulatory Compliance: All study activities must comply with local and national health regulations.

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List of participating clinical trials sites

Alabama Locations

Mobile, Alabama, United States, 36604

Recruiting: USA Health Strada Patient Care Center
Contact: Site Public Contact, 800-388-8721
Principal Investigator: Hamayun Imran

Alaska Locations

Anchorage, Alaska, United States, 99508

Recruiting: Providence Alaska Medical Center
Contact: Site Public Contact, 907-212-6871, AKPAMC.OncologyResearchSupport@providence.org
Principal Investigator: Nitya Alluri

Arizona Locations

Goodyear, Arizona, United States, 85338

Recruiting: CTCA at Western Regional Medical Center
Contact: Site Public Contact, 623-207-3000
Principal Investigator: Jeffrey R. Schriber

Arkansas Locations

Little Rock, Arkansas, United States, 72202-3591

Recruiting: Arkansas Children's Hospital
Contact: Site Public Contact, 501-364-7373
Principal Investigator: David L. Becton

California Locations

Downey, California, United States, 90242

Recruiting: Kaiser Permanente Downey Medical Center
Contact: Site Public Contact, 626-564-3455
Principal Investigator: Robert M. Cooper

Duarte, California, United States, 91010

Recruiting: City of Hope Comprehensive Cancer Center
Contact: Site Public Contact, 800-826-4673, becomingapatient@coh.org
Principal Investigator: Alex F. Herrera

Irvine, California, United States, 92618

Recruiting: City of Hope at Irvine Lennar
Contact: Site Public Contact, 877-467-3411
Principal Investigator: Alex F. Herrera

Loma Linda, California, United States, 92354

Recruiting: Loma Linda University Medical Center
Contact: Site Public Contact, 909-558-4050
Principal Investigator: Albert Kheradpour

Long Beach, California, United States, 90806

Recruiting: Miller Children's and Women's Hospital Long Beach
Contact: Site Public Contact, 562-933-5600
Principal Investigator: Jacqueline N. Casillas

Los Angeles, California, United States, 90027

Recruiting: Children's Hospital Los Angeles
Contact: Site Public Contact, 323-361-4110
Principal Investigator: Andrew Doan

Los Angeles, California, United States, 90048

Recruiting: Cedars Sinai Medical Center
Contact: Site Public Contact, 310-423-8965
Principal Investigator: Nicole M. Baca

Oakland, California, United States, 94611

Recruiting: Kaiser Permanente-Oakland
Contact: Site Public Contact, 877-642-4691, Kpoct@kp.org
Principal Investigator: Aarati V. Rao

Orange, California, United States, 92868

Recruiting: Children's Hospital of Orange County
Contact: Site Public Contact, 714-509-8646, oncresearch@choc.org
Principal Investigator: Elyssa M. Rubin

San Diego, California, United States, 92123

Recruiting: Rady Children's Hospital - San Diego
Contact: Site Public Contact, 858-966-5934
Principal Investigator: William D. Roberts

South Pasadena, California, United States, 91030

Recruiting: City of Hope South Pasadena
Contact: Site Public Contact, 800-826-4673, becomingapatient@coh.org
Principal Investigator: Alex F. Herrera

Upland, California, United States, 91786

Recruiting: City of Hope Upland
Contact: Site Public Contact, 800-826-4673, becomingapatient@coh.org
Principal Investigator: Alex F. Herrera

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Any other information

Link to clinicaltrials.gov

Comparing Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab, in 5-60 year old patients