Brentuximab Vedotin for Hodgkin Lymphoma

(RADAR Trial)

Recruiting at 58 trial locations

Overseen By RADAR Trial Coordinator

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: University College, London

Must not be taking: Antibiotics, Antivirals, Antifungals, others

Disqualifiers: Other cancer, Neuropathy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12-16 weeks

1042 Participants Needed

Trial Summary

What is the purpose of this trial?

RADAR is a multicentre, international, randomised, open-label phase III clinical trial composed of 2 trials running in parallel. Trial 1 will be led and sponsored by University College London (UCL) and conducted in Europe and Australia/New Zealand. Trial 2 will be led by the Canadian Cancer Trials Group (CCTG) and conducted in North America, with CCTG the regulatory sponsor in Canada, and University of Miami the regulatory sponsor and IND holder in the US. Datasets from Trial 1 and Trial 2 will be combined to achieve the total sample size. Data analysis will be performed by UCL and therefore UCL is responsible for the clinicaltrials.gov entry. Eligible patients will be randomised to receive either ABVD or A2VD chemotherapy. An interim PET-CT scan will be performed after 2 cycles of treatment, which will be used to adapt subsequent treatment. Patients will receive a total of 3-4 cycles of chemotherapy and may also receive involved site radiotherapy as consolidation. Patients will be followed up for a minimum of 5 years after treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on any investigational agents, you must stop them at least 4 weeks before joining the trial.

What data supports the effectiveness of the drug Brentuximab Vedotin for Hodgkin Lymphoma?

Brentuximab Vedotin has shown high response rates in patients with relapsed or refractory Hodgkin Lymphoma, with studies reporting up to 75% objective response rates. It is effective in reducing tumor size and prolonging progression-free survival, making it a promising option for patients who have limited treatment choices. ^{1 2 3 4 5}

Is Brentuximab Vedotin safe for humans?

Brentuximab Vedotin has been generally well tolerated in clinical trials for Hodgkin lymphoma and other CD30-positive cancers, with common side effects including peripheral neuropathy (nerve damage causing tingling or numbness) and neutropenia (low white blood cell count). Most side effects were manageable with dose adjustments, and the treatment did not cause significant heart rhythm changes. ^{1 5 6 7 8}

What makes the drug Brentuximab Vedotin unique for treating Hodgkin Lymphoma?

Brentuximab Vedotin is unique because it is an antibody-drug conjugate specifically targeting CD30-positive cancer cells, which are common in Hodgkin Lymphoma. It has shown high response rates in patients who have relapsed after other treatments, and it can be used as a consolidation therapy to prolong progression-free survival after stem cell transplants. ^{1 5 9 10 11}

Research Team

John Radford

Principal Investigator

University of Manchester / Christie Hospital, Manchester

Eligibility Criteria

This trial is for individuals aged 16-69 with early stage Hodgkin lymphoma who haven't had treatment before. They must be physically fit, have normal organ function, and agree to follow the study's rules including contraceptive advice. Excluded are those allergic to trial drugs, pregnant or breastfeeding women, over age 70 or under age 15, with certain infections or other serious health issues.

Inclusion Criteria

I can take care of myself and perform daily activities.

I have not received any treatment for Hodgkin lymphoma.

ALT or AST < 2 x upper limit of normal

Exclusion Criteria

You have allergies to certain proteins or ingredients found in the study drug brentuximab vedotin or its components.

I do not have any severe health or mental conditions that would make cancer treatment risky.

I have been diagnosed with a type of lymphoma called nodular lymphocyte predominant Hodgkin lymphoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ABVD or A2VD chemotherapy for 3-4 cycles, with PET-CT scans to adapt treatment based on Deauville score

12-16 weeks

Multiple visits for chemotherapy administration and PET-CT scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular follow-up visits

Radiotherapy (if applicable)

Involved site radiotherapy is administered for patients with Deauville score 4 after chemotherapy

4-6 weeks

Treatment Details

Interventions

• Brentuximab Vedotin
• Dacarbazine

Trial Overview The RADAR trial tests ABVD versus A2VD chemotherapy regimens in patients with Hodgkin lymphoma. It includes an interim PET-CT scan after two cycles of chemo to adjust further treatment. Participants may also receive radiotherapy and will be followed up for at least five years post-treatment.

Participant Groups

Group I: A2VD +/- ISRT Experimental Treatment 6 Interventions

2 x 28 day cycles of A2VD: Doxorubicin 25mg/m\^2 IV days 1 \& 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 \& 15 Vinblastine 6mg/m\^2 days 1 \& 15 Dacarbazine 375mg/m\^2 days 1 \& 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 \& 16) PET-CT after 2 cycles will determine subsequent treatment: Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.

Group II: ABVD +/- ISRT Active Control 5 Interventions

2 x 28 day cycles of ABVD: Doxorubicin 25mg/m\^2 IV days 1 \& 15 Bleomycin 10000 IU/m\^2 days 1 \& 15 Vinblastine 6mg/m\^2 days 1 \& 15 Dacarbazine 375mg/m\^2 days 1 \& 15 PET-CT after 2 cycles will determine subsequent treatment: Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

University College, London

Lead Sponsor

Trials

884

Recruited

38,770,000+

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

University of Miami

Collaborator

Trials

976

Recruited

423,000+

European Organisation for Research and Treatment of Cancer - EORTC

Collaborator

Trials

417

Recruited

166,000+

Australasian Leukaemia and Lymphoma Group

Collaborator

Trials

17

Recruited

4,300+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Findings from Research

Brentuximab vedotin is an effective treatment for relapsed or refractory classical Hodgkin lymphoma, showing high response rates and durable outcomes in both clinical trials and real-world settings.

In the phase 3 AETHERA trial, brentuximab vedotin significantly prolonged progression-free survival compared to placebo after autologous stem cell transplant, reducing the risk of disease progression or death by 43% over a median follow-up of 30 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Scott, LJ.[2020]

Brentuximab vedotin, an antibody-drug conjugate, has shown impressive response rates of 75% in relapsed/refractory Hodgkin's lymphoma and 87% in relapsed/refractory systemic anaplastic large-cell lymphoma in large Phase II trials.

The treatment is well tolerated with manageable side effects, primarily peripheral sensory neuropathy, making it a promising option for patients with limited treatment choices and potential for use in front-line therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin for the treatment of CD30+ lymphomas. Foyil, KV., Bartlett, NL.[2021]

Brentuximab vedotin, an antibody-drug conjugate, shows a high response rate of 75% in relapsed/refractory Hodgkin lymphoma, but resistance often develops due to upregulation of the MDR1 protein.

Combining brentuximab vedotin with cyclosporine A (CsA) effectively restores sensitivity to the drug in resistant cases, achieving a 75% overall response rate and 42% complete response rate in a phase I trial, indicating a promising new strategy to overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma. Chen, R., Herrera, AF., Hou, J., et al.[2021]

In a study of 234 patients with relapsed Hodgkin's lymphoma, brentuximab vedotin (BV) demonstrated a significant overall response rate of 48.3%, with 31.6% achieving a complete response after a median of 4 treatment cycles.

The treatment was well tolerated with no deaths linked to BV toxicity, and it was particularly effective in elderly patients, confirming its role as a viable option for bridging to transplant in chemorefractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian real life experience with brentuximab vedotin: results of a large observational study on 234 relapsed/refractory Hodgkin's lymphoma. Pellegrini, C., Broccoli, A., Pulsoni, A., et al.[2019]

Brentuximab vedotin demonstrated a high overall objective response rate of 75% in 102 patients with relapsed Hodgkin lymphoma and 86% in 58 patients with relapsed systemic anaplastic large cell lymphoma, indicating its efficacy as a targeted treatment.

The treatment was generally well tolerated, with peripheral neuropathy being the most common side effect; however, about half of the patients who experienced this side effect saw complete resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Garnock-Jones, KP.[2021]

Brentuximab vedotin, an antibody-drug conjugate used for treating certain lymphomas, showed improved progression-free survival in patients with cutaneous T-cell lymphoma (CTCL) without a direct correlation to the drug's exposure levels, indicating its efficacy is consistent across different exposure ranges.

The study found that while higher exposure to the drug was linked to an increase in severe treatment-emergent adverse events (TEAEs), the results support the use of a standard dose of 1.8 mg/kg every 3 weeks, with the option for dose reductions in patients experiencing significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. Suri, A., Mould, DR., Liu, Y., et al.[2019]

Brentuximab vedotin, an antibody-drug conjugate, does not cause significant prolongation of the QT/QTc interval, indicating a favorable cardiac safety profile in patients with CD30-positive hematologic malignancies.

In a phase 1 study involving 52 patients, brentuximab vedotin was well tolerated, with no clinically meaningful changes in cardiac repolarization and a response rate consistent with previous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. Han, TH., Chen, R., Advani, R., et al.[2021]

In a phase 2 study involving 41 patients with untreated HIV-associated classical Hodgkin lymphoma, brentuximab vedotin combined with AVD showed a high complete response rate of 100% among those who completed therapy, with a 2-year progression-free survival rate of 87%.

The treatment was generally well-tolerated, with the most common serious side effects being neutropenia and peripheral sensory neuropathy, indicating that brentuximab vedotin-AVD is a promising and safe option for patients with HIV-cHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial. Rubinstein, PG., Moore, PC., Bimali, M., et al.[2023]

Brentuximab vedotin is an antibody-drug conjugate that combines an anti-CD30 antibody with a powerful cytotoxic agent, showing promise in treating Hodgkin lymphoma and anaplastic large cell lymphoma.

The drug is currently under investigation in North America and Europe, highlighting its potential as a targeted therapy for specific types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

In a phase 1 trial involving 7 patients with HIV-associated classical Hodgkin lymphoma, the combination of brentuximab vedotin and AVD was well tolerated at a dose of 1.2 mg/kg, with no dose-limiting toxicities identified and a 100% progression-free survival rate at 25 months.

The study highlighted the importance of avoiding strong CYP3A4 inhibitors during treatment, as one patient who took ritonavir experienced severe adverse events, underscoring the need for careful medication management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. Rubinstein, PG., Moore, PC., Rudek, MA., et al.[2020]

A 23-year-old female with stage IV Hodgkin lymphoma experienced severe anaphylaxis after her fifth cycle of brentuximab vedotin, highlighting the potential for serious hypersensitivity reactions in patients receiving this treatment.

Successful desensitization allowed her to continue treatment without further hypersensitivity reactions, suggesting that rapid desensitization protocols can be effective and may improve survival rates compared to switching to second-line therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid desensitization to brentuximab vedotin after severe anaphylaxis in the treatment of refractory Hodgkin's lymphoma. V Villarreal-Gonzalez, R., N Gonzalez-Diaz, S., E de Lira-Quezada, C., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin for the treatment of CD30+ lymphomas. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Italian real life experience with brentuximab vedotin: results of a large observational study on 234 relapsed/refractory Hodgkin's lymphoma. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Rapid desensitization to brentuximab vedotin after severe anaphylaxis in the treatment of refractory Hodgkin's lymphoma. [2021]