Radiolabeled Monoclonal Antibody + Chemotherapy Before Stem Cell Transplant for Hodgkin Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Disqualifiers: Lymphocyte-predominant HL, Prior transplants, Active hepatitis, HIV, Myelodysplasia, others

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

Compensation: Varies

Number of Visits: 90

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of a new treatment that combines radiolabeled monoclonal antibody therapy with chemotherapy for Hodgkin lymphoma. The treatment specifically targets cancer cells while sparing healthy ones, potentially benefiting patients whose cancer hasn't responded to standard treatments or has recurred. Participants should have Hodgkin lymphoma that did not respond to initial treatment or has returned after treatment, with evidence of the disease from scans or a biopsy. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Past studies have shown that radiolabeled monoclonal antibody therapy is safe and tolerable for patients with similar conditions, meaning most patients did not experience severe side effects. Research indicates that combining this therapy with BEAM chemotherapy (a mix of drugs that stop cancer cells) was effective and safe in other trials.

Carmustine can cause serious lung problems, so doctors must carefully weigh the risks and benefits for each patient. Cytarabine is generally safe, with only minor side effects reported, and serious issues are rare.

Etoposide has been used for many years, and while it can have side effects, they are usually manageable. Melphalan is also widely used for similar cancer treatments and is considered safe, though it can have side effects like all cancer drugs.

This trial is in the early stages, so researchers are primarily focused on finding the safest dose and understanding the side effects of the new combination with radiolabeled monoclonal antibodies. Safety data is still being collected, but past studies of the individual treatments provide some reassurance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for Hodgkin Lymphoma because it combines a radiolabeled monoclonal antibody with chemotherapy, offering a unique approach. Most treatments rely on chemotherapy alone, but this approach uses an antibody tagged with a radioactive particle to directly target cancer cells, sparing more healthy tissue. This targeted action could potentially make the treatment more effective and reduce side effects compared to standard chemotherapy regimens. Additionally, incorporating a radiolabeled component may enhance the ability to deliver radiation directly to cancer cells, offering a promising advancement in treatment efficacy.

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

In this trial, participants will receive radiolabeled monoclonal antibody therapy using yttrium-90 basiliximab, which may be effective for Hodgkin lymphoma. This treatment targets cancer cells while sparing normal cells. Studies have found that a similar treatment, 90Y-daclizumab, helped 50% of patients with recurring Hodgkin's lymphoma. Participants will also receive a chemotherapy regimen known as BEAM, which includes carmustine, etoposide, cytarabine, and melphalan. These drugs effectively stop cancer cells from growing and spreading. For instance, etoposide showed an 84% success rate in some studies. Together, these treatments aim to eliminate more cancer cells before a stem cell transplant. ^{6 7 8 9 10}

Who Is on the Research Team?

Eileen Smith

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with Hodgkin lymphoma that didn't respond to initial treatment or came back after therapy. Participants must have acceptable organ function, not be pregnant or breastfeeding, agree to use birth control, and have collected enough stem cells for transplant. They should not have had certain previous treatments like high-dose chemo with stem cell transplant or radiation to critical organs.

Inclusion Criteria

Hodgkin lymphoma that is:

Pathology confirmation of HL with City of Hope (COH) pathology review

PIF (primary induction failure): did not enter complete remission with first line of therapy; Note: a patient with PIF who responds to salvage therapy with a PR or CR is also eligible (and would be considered PIF-sensitive)

Exclusion Criteria

Positive human immunodeficiency virus antibody

Lymphocyte-predominant Hodgkin lymphoma

Prior high dose chemotherapy with autologous stem cell transplant, or prior allogeneic transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosimetry Study

Patients receive basiliximab IV and indium In 111 basiliximab IV on day -21 and undergo imaging scans to determine biodistribution

3 weeks

Daily imaging visits

Treatment

Patients receive basiliximab IV and yttrium Y 90 basiliximab IV on day -14, followed by BEAM chemotherapy and autologous hematopoietic progenitor cell infusion

3 weeks

Multiple in-person visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Visits at day 90-100, 180, 1 year, 1.5 years, and annually up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Basiliximab
• Carmustine
• Cytarabine
• Etoposide
• Melphalan
• Radiolabeled Monoclonal Antibody Therapy
• Yttrium Y 90-labeled basiliximab

Trial Overview The study tests a radiolabeled monoclonal antibody (yttrium Y 90-labeled basiliximab) combined with BEAM chemotherapy before a stem cell transplant in patients whose Hodgkin lymphoma has relapsed or was resistant from the start. The goal is to see how well this approach works and what the best dose of the antibody therapy might be.

How Is the Trial Designed?

Group I: Treatment (radiolabeled monoclonal antibody, chemotherapy) Experimental Treatment 9 Interventions

DOSIMETRY STUDY: Patients receive basiliximab IV and indium In 111 basiliximab IV on day -21. Patients undergo indium In 111 imaging scans daily. Patients with appropriate biodistribution continue on to treatment. TREATMENT: Patients receive basiliximab IV and yttrium Y 90 basiliximab IV on day -14. Patients also receive BEAM chemotherapy comprising carmustine IV over 2 hours on days -7 and -6, etoposide IV BID over 4 hours and cytarabine IV over 2 hours BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic progenitor cell infusion on day 0.

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28112752/

Carmustine replacement in intensive chemotherapy ... The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM).

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

Carmustine for Lymphoma Carmustine (BCNU) is part of standard treatment regimens like BEAM and BEAC for lymphoma, which have shown effectiveness and low nonrelapse mortality. These ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1465324924000446

Prognostic differences between carmustine, etoposide ... The powerful efficacy and good safety of ASCT plus CART therapy can be attributed to a high-dose conditioning regimen and hematopoietic stem cell transplant.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25563428/

High-dose chemotherapy with carmustine, etoposide, ... We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, ...

5. ashpublications.org ashpublications.org/blood/article/118/21/2023/68483/Comparison-of-Toxicity-and-Outcomes-of-BCNU

Comparison of Toxicity and Outcomes of BCNU-Containing ... We retrospectively compared the two types of conditioning regimens for toxicity, efficacy and outcome. Methods: One hundred and fifty five ...

6. 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: ...

7. 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 ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/carmustine-intravenous-route/description/drg-20067151

Carmustine (intravenous route) - Side effects & uses Safety and efficacy have not been established. Geriatric. No information is available on the relationship of age to the effects of carmustine ...

9. 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.

10. bccancer.bc.ca bccancer.bc.ca/drug-database-site/Drug%20Index/Carmustine%20monograph.pdf

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