Radioimmunotherapy + BEAM Chemotherapy for Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Myelodysplasia, Active malignancy, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: 30

Duration: 14 days

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating Hodgkin's lymphoma that resists standard treatments or recurs after treatment. It combines a radioactive antibody (Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody) targeting cancer cells with several chemotherapy drugs to kill the cancer and prepare the body for a stem cell transplant. Suitable candidates for this trial have Hodgkin's lymphoma that did not resolve with initial treatment or returned within a year. The goal is to determine if this combination can shrink or eliminate tumors more effectively and support recovery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to benefit from innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown the yttrium-90 labeled anti-CD25 monoclonal antibody to be relatively safe. For instance, 90Y-daclizumab, a similar antibody, helped 50% of patients with relapsed Hodgkin's lymphoma.

Carmustine, however, carries some known risks, such as lung problems like scarring or fluid build-up, particularly with long-term use.

Etoposide is generally well-tolerated. One study successfully used it in 94% of patients to aid in stem cell collection.

These treatments have been used before, and the current trial is in phase 2. Researchers have some safety data but continue to gather more information on tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for Hodgkin's Lymphoma because it combines radioimmunotherapy with BEAM chemotherapy, offering a unique approach compared to standard treatments like ABVD or Stanford V. This treatment uses Yttrium-90 labeled anti-CD25 monoclonal antibodies, which specifically target and destroy cancerous cells, potentially reducing damage to healthy tissues. Additionally, the use of radioimmunotherapy allows for a more precise delivery of radiation, potentially increasing effectiveness and minimizing side effects. These innovative features could offer new hope for patients with Hodgkin's Lymphoma by enhancing treatment efficacy and improving outcomes.

What evidence suggests that this trial's treatments could be effective for Hodgkin's Lymphoma?

In this trial, participants will receive a treatment regimen that includes yttrium-90, a radioactive substance attached to an antibody. Research has shown that yttrium-90 can help half of the patients with relapsed Hodgkin's lymphoma by targeting and killing cancer cells. The trial also includes the chemotherapy drugs Carmustine and Etoposide. Carmustine, part of standard treatments, helps patients live longer without disease recurrence. Etoposide effectively treats relapsed lymphoma and prepares blood-forming cells for transplantation. Together, these treatments aim to target and reduce cancer cells in Hodgkin's lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Alex F. Herrera

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with Hodgkin lymphoma that hasn't improved or has returned after treatment can join this trial. They must have a life expectancy of at least 6 months, be in good physical condition, and have collected enough stem cells for transplant. People who've had certain previous treatments, significant organ damage from radiation, active hepatitis B or C, HIV with low CD4 counts, pregnancy, or other serious health issues cannot participate.

Inclusion Criteria

My Hodgkin's lymphoma has returned after two treatments and I'm not in complete remission.

My first cancer remission lasted between 3 and 12 months after my initial treatment.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

My bone marrow still shows over 10% involvement with Hodgkin's Lymphoma after initial treatment.

I have had a stem cell transplant before.

Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by P.I.)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV, BEAM chemotherapy, and HPC-A infusion

14 days

Daily visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular follow-up visits at 30 days, up to 2 years for response, and up to 5 years for survival

What Are the Treatments Tested in This Trial?

Interventions

• Autologous stem cell transplantation
• Carmustine
• Etoposide
• Yttrium - 90 Basiliximab
• Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody

Trial Overview The trial is testing a radioactive antibody called Yttrium-90 Basiliximab combined with BEAM chemotherapy (carmustine, etoposide, cytarabine) before stem cell transplant in patients with stubborn or returning Hodgkin lymphoma. The goal is to see if this combo can better kill cancer cells and make space for new blood-forming cells to grow.

How Is the Trial Designed?

Group I: Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Experimental Treatment 7 Interventions

Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement.

Carmustine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as BiCNU for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Approved in European Union as Carmubris for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Approved in Canada as BCNU for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Radioimmunotherapy using (90)Y-ibritumomab-tiuxetan is an effective treatment for non-Hodgkin's lymphoma, specifically targeting B-lymphocytes with a monoclonal antibody conjugated to a radioisotope.

Originally indicated for relapsed low-grade non-Hodgkin's lymphoma, this treatment has been explored in clinical trials for various lymphoma types and as a preparatory step before stem cell transplantation, indicating its potential versatility in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Indications for radioimmunotherapy for patients with non-Hodgkin's lymphoma]. Frølund, UC., Hansen, PB.[2018]

Yttrium 90 (Y-90) ibritumomab tiuxetan is an effective radioimmunotherapy for treating relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma, including cases resistant to rituximab.

This treatment can be safely administered in an outpatient setting with minimal radiation safety restrictions, making it convenient for both patients and healthcare workers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation safety guidelines for radioimmunotherapy with yttrium 90 ibritumomab tiuxetan. Hendrix, C.[2016]

In a clinical trial involving 16 patients with high-tumor-burden follicular lymphoma, the overall response rate to Yttrium 90-ibritumomab tiuxetan (90Y-IT) was 69%, with significant myelosuppression observed as the major toxicity, affecting 88% of patients with grade 3 and 31% with grade 4 hematologic toxicity.

The study found that maintenance rituximab after 90Y-IT improved outcomes, converting all partial responses to complete responses, and while the median progression-free survival has not been reached, the 3-year rates were 56% for progression-free survival and 93% for overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium 90-ibritumomab tiuxetan plus rituximab maintenance as initial therapy for patients with high-tumor-burden follicular lymphoma: a Wisconsin Oncology Network study. Rajguru, S., Kristinsdottir, T., Eickhoff, J., et al.[2016]

Yttrium-90 ibritumomab tiuxetan (Zevalin) is an effective treatment for relapsed or refractory B-cell non-Hodgkin's lymphoma, with a significant number of patients (37%) achieving long-term durable responses lasting over 12 months.

In a study of 211 patients, those who had previously failed multiple treatments still experienced median time to progression of 29.3 months, indicating that prior treatment failures do not prevent successful outcomes with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) induces long-term durable responses in patients with relapsed or refractory B-Cell non-Hodgkin's lymphoma. Wiseman, GA., Witzig, TE.[2016]

In a phase II trial involving 41 patients with non-Hodgkin's lymphoma, the combination of yttrium-90 ibritumomab tiuxetan with high-dose BEAM chemotherapy and autologous stem-cell transplantation showed promising efficacy, with a 2-year overall survival rate of 88.9% and a progression-free survival rate of 69.8%.

The safety profile of this combination treatment was comparable to that of high-dose BEAM alone, with adverse events primarily consisting of grade 3 or 4 pulmonary toxicity in 10 patients, indicating that the addition of 90Y ibritumomab tiuxetan is feasible for patients ineligible for total-body irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a transplantation regimen of yttrium-90 ibritumomab tiuxetan and high-dose chemotherapy in patients with non-Hodgkin's lymphoma. Krishnan, A., Nademanee, A., Fung, HC., et al.[2016]

In a study of 19 patients with relapsed or refractory B-cell non-Hodgkin's lymphoma, the combination of yttrium-90-ibritumomab with a conditioning regimen of busulfan, cyclophosphamide, and etoposide (Bu/Cy/E) before autologous stem cell transplantation (ASCT) resulted in a high overall response rate of 84.2%.

The treatment was found to be safe, with adverse events comparable to those historically associated with Bu/Cy/E alone, and no treatment-related deaths were reported, indicating that this combination therapy does not increase toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90-ibritumomab tiuxetan in combination with intravenous busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Kang, BW., Kim, WS., Kim, C., et al.[2021]

Yttrium 90 ibritumomab tiuxetan is an effective treatment for patients with B-cell non-Hodgkin's lymphoma, demonstrating a good safety profile and being well tolerated by patients.

Unlike conventional chemotherapy and external beam radiation therapy, 90Y ibritumomab tiuxetan is not associated with the same adverse events, making it a safer alternative for treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin). Riley, MB., Gordon, LI.[2019]

In a phase I study involving patients with relapsed or refractory low-grade or transformed CD20+ B-cell non-Hodgkin lymphoma, a combination of rituximab followed by Yttrium-90 (⁹⁰Y)-ibritumomab tiuxetan resulted in an 82% overall response rate, with complete clearance of bone marrow involvement in 50% of patients.

The study found that while the treatment was effective, it also led to significant hematologic toxicity, with 80% of patients experiencing grade-4 cytopenias at the higher dose of 0.4 mCi/kg, indicating a need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of a modified regimen of ⁹⁰Yttrium-ibritumomab tiuxetan for relapsed or refractory follicular or transformed CD20+ non-Hodgkin lymphoma. Vaklavas, C., Meredith, RF., Shen, S., et al.[2020]

In a phase 2 trial involving 104 elderly patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), a single dose of yttrium-90 ibritumomab tiuxetan showed an overall response rate of 52% in patients whose induction therapy had failed and 53% in those who relapsed after complete response, indicating its efficacy in this patient population.

The treatment resulted in median overall survival rates of 21.4 months and 22.4 months for patients in the failed induction and relapsed groups, respectively, while nonhematologic adverse events were generally mild to moderate, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Morschhauser, F., Illidge, T., Huglo, D., et al.[2021]

Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) is an effective targeted radiation therapy for treating B-cell non-Hodgkin's lymphoma, with established therapeutic doses of 0.4 mCi/kg for low-grade NHL.

Ongoing trials are exploring various dosing schedules and combinations with chemotherapy and stem cell transplantation to enhance treatment response and duration, indicating the potential for improved survival rates in patients with NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non-Hodgkin's lymphoma. Micallef, IN.[2019]

Monoclonal antibodies, particularly rituximab, have been effective in treating relapsed or refractory non-Hodgkin's lymphoma, but improvements are needed for better treatment outcomes.

Recent developments in radiolabeled immunoconjugates, such as ibritumomab linked to yttrium-90, show promise in enhancing therapeutic efficacy compared to non-radioactive treatments, with ongoing research into optimizing targeting and using alpha radiation for better results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy of non-Hodgkin's lymphoma: molecular targeting and novel agents. Pauwels, EK., Erba, P.[2007]

In a study of 77 patients with relapsed or refractory low-grade B-cell lymphomas, the combination of yttrium-90 ibritumomab tiuxetan and the BEAM regimen before autologous stem cell transplantation resulted in a high complete response rate of 77% before transplantation and 88% three months post-transplant.

The treatment showed promising long-term outcomes, with a 2-year event-free survival rate of 63% and an overall survival rate of 97%, indicating its potential efficacy and safety for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(90)Y ibritumomab tiuxetan (Zevalin) combined with BEAM (Z -BEAM) conditioning regimen plus autologous stem cell transplantation in relapsed or refractory low-grade CD20-positive B-cell lymphoma. A GELA phase II prospective study. Decaudin, D., Mounier, N., Tilly, H., et al.[2015]

In a phase III study involving 143 patients with relapsed or refractory non-Hodgkin's lymphoma, radioimmunotherapy using yttrium-90 ibritumomab tiuxetan achieved an overall response rate of 80%, significantly higher than the 56% response rate seen with rituximab alone.

The treatment with yttrium-90 ibritumomab tiuxetan also resulted in a higher complete response rate (30% vs. 16% for rituximab), demonstrating its efficacy as a therapeutic option, while being well tolerated with manageable side effects like reversible myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. Witzig, TE., Gordon, LI., Cabanillas, F., et al.[2022]

Citations

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High-dose carmustine, etoposide, and cisplatin for ... Thirty-two patients had indolent (low-grade), 42 had aggressive (intermediate-grade), and 27 had very aggressive (high-grade) non-Hodgkin lymphoma. Thirty-six ...

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High-Dose Carmustine, Etoposide, and ... Based on the results of these studies, it is apparent that a subset of patients achieve long-term disease-free survival with allogeneic HCT despite recurrent, ...

3. withpower.com withpower.com/trial/carmustine-for-lymphoma-e04cc

Carmustine for Lymphoma What data supports the effectiveness of the drug BiCNU (carmustine) for treating lymphoma? Carmustine (BCNU) is part of standard treatment regimens like ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636722016980

Transplantation and Cellular Therapy As novel therapies emerge, autologous stem cell transplantation allows for prolonged disease-free survival in patients with chemosensitive lymphoma.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3635682/

Phase III Randomized Study of Rituximab/Carmustine ... Herein, we report the results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0401 study, which was a phase III trial comparing outcomes of ...

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DRUG NAME: Carmustine Pulmonary fibrosis and pulmonary infiltrates can occur with carmustine injection. Pulmonary toxicities 28 are more common with prolonged therapy ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/017422s038lbl.pdf

BICNU (carmustine) injection label - accessdata.fda.gov Therefore, the risks and benefits of BiCNU therapy must be carefully considered, due to the extremely high risk of pulmonary toxicity. (See ADVERSE. REACTIONS: ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6103227/

Comparable safety profile of BeEAM (bendamustine, ... Clinical characteristics of both groups were comparable. Patients with Hodgkin's lymphoma (HL) constituted 49% of the BEAM group and 40% of the BeEAM group.

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK548307/

Carmustine - LiverTox - NCBI Bookshelf - NIH Carmustine therapy is associated with minor transient serum enzyme elevations and has been linked to cases of acute liver injury including cholestatic ...

10. healio.com healio.com/clinical-guidance/drugs/bicnu

BiCNU: Uses, Side Effects & Dosage Find clinical guidance on BiCNU, including indications, dosing, safety, side effects and evidence-based insights for healthcare professionals.