Radioimmunotherapy for Benign Conditions

Overseen By Phuong Vo

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Antihypertensives, Cardiac medications

Disqualifiers: Fanconi anemia, HIV, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 5 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for patients with non-cancerous diseases requiring a stem cell transplant. The researchers aim to determine the optimal dose of a new radioactive treatment, Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10, combined with whole-body radiation (Total-Body Irradiation), to prepare patients for donor stem cells. This approach may prevent the immune system from rejecting donor cells and inhibit unwanted cell growth. Individuals with non-cancerous diseases treatable by stem cell transplant might be suitable candidates, particularly if evaluated by a gastrointestinal specialist. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's effects in people and assess its efficacy in an initial, smaller group, offering participants the opportunity to contribute to groundbreaking medical advancements.

Do I have to stop taking 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 this with the trial coordinators or your doctor.

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

Research has shown that the astatine-211-labeled anti-CD45 monoclonal antibody is generally well-tolerated by patients. In studies, patients responded well to specific doses and energy levels. For instance, doses between 0.75 and 0.5 mg per kilogram of body weight and energy levels between 8.436 and 22.792 MBq were used without major issues.

This antibody specifically targets CD45-positive cells, ensuring the treatment reaches the intended cells. This targeted approach aims to minimize harm to healthy cells. The treatment has also undergone testing to confirm its sterility and safety, crucial steps before administration to people. While further research is necessary, these findings suggest that the treatment can be safely administered at certain levels. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach for benign conditions using radioimmunotherapy. Unlike traditional treatments, which may involve surgery or conventional radiation, this method uses a unique active ingredient: astatine At 211, a radioactive element that targets specific cells with precision. This targeted approach aims to minimize damage to healthy tissues, potentially reducing side effects compared to existing therapies. Additionally, combining this with other agents like fludarabine and cyclophosphamide, along with total-body irradiation and a hematopoietic cell transplant, could enhance treatment effectiveness and improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for nonmalignant diseases?

Research has shown that the astatine-211-labeled BC8-B10 monoclonal antibody targets a protein called CD45, present on certain cells. This targeting allows it to deliver a dose of alpha radiation directly to these cells, effectively killing cancerous and harmful cells. Early results from related studies indicated a one-year overall survival rate of 43% and a recurrence-free survival rate of 35%. These findings suggest that the treatment may help reduce tumor size and improve survival chances. In this trial, participants will receive a combination of treatments, including the astatine-211-labeled BC8-B10 monoclonal antibody and total body irradiation, to prepare for stem cell transplants, potentially lowering the risk of transplant rejection. ^{1 2 5 6 7}

Who Is on the Research Team?

Phuong Vo

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults under 50 with benign tumors treatable by stem cell transplant. They must have good performance scores, normal organ function, and a suitable donor (related or unrelated) matched to their HLA type. Pregnant or breastfeeding women, those unwilling to use contraception, and individuals with certain heart, lung, kidney or liver conditions are excluded.

Inclusion Criteria

DONOR INCLUSION

My donor matches me closely in immune system markers, with at most one mismatch allowed.

I am mostly active and can care for myself.

Exclusion Criteria

My heart function is normal, and I don't need medication for heart failure or uncontrolled high blood pressure.

My liver function is not severely impaired.

I am not willing to use birth control during and for a year after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10, fludarabine, cyclophosphamide, thymoglobulin, and undergo total body irradiation and hematopoietic cell transplant

Approximately 5 weeks

Multiple visits for IV administration and procedures

Post-Transplant Medication

Participants receive mycophenolate mofetil and sirolimus to prevent graft-versus-host disease

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Periodic visits

What Are the Treatments Tested in This Trial?

Interventions

• Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
• Total-Body Irradiation

Trial Overview The trial tests total body irradiation combined with Astatine-211-labeled BC8-B10 monoclonal antibody before hematopoietic cell transplantation in patients with nonmalignant diseases. It aims to find the best dose of radiation therapy that targets cancer cells without harming the patient's immune system.

How Is the Trial Designed?

Group I: Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT) Experimental Treatment 10 Interventions

Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 IV on any day between days -10 and -7, fludarabine IV on days -6 to -2, cyclophosphamide IV over 1 hour on days -6 to -5 and 3 to 4, and thymoglobulin IV over 4-6 hours on days -4 to -2. Patients undergo TBI on day -1 and hematopoietic cell transplant on day 0. Beginning day 5, patients also receive mycophenolate mofetil PO or IV thrice daily every 8 hours up to day 35 if no GVHD present and sirolimus PO daily until day 365. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30335787/

cGMP production of astatine-211-labeled anti-CD45 ... - PubMed The objective of this study was to translate reaction conditions and quality control methods used for production of an astatine-211(211At)-labeled anti-CD45 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04083183?term=astatine&rank=3

Total Body Irradiation and Astatine-211-Labeled BC8-B10 ... This phase I/II trial studies the best dose of total body irradiation with astatine-211 BC8-B10 monoclonal antibody for the treatment of patients with ...

3. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/astatine-at-211-anti-cd45-monoclonal-antibody-bc8-b10

astatine At 211 anti-CD45 monoclonal antibody BC8-B10 After binding and internalization by CD45-expressing tumor cells, this agent may deliver a cytotoxic dose of alpha radiation.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9859440/

Astatine-211 based radionuclide therapy: Current clinical trial ... The authors concluded that the preliminary efficacy data of a 1-year overall survival of 43% and recurrence-free survival of 35% support further exploration of ...

5. openmedscience.com openmedscience.com/astatine-211-bc8-b10-a-promising-radioimmunoconjugate-for-leukaemia-treatment/

Astatine-211 BC8-B10 for Leukaemia Prospective Outcomes. The clinical trials aim to assess the effectiveness of Astatine-211 BC8-B10 in reducing tumour burden and improving survival rates in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6193629/

cGMP production of astatine-211-labeled anti-CD45 ... The vialed BC8-B10 was examined by SE-HPLC, SDS-PAGE and IEF for identity; tested for sterility, endotoxin and general safety; and functionality ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/65/9/1443

211At-Labeled Anti-CD45 Antibody as a Nonmyeloablative ... At-CD45-B10 was well tolerated and effective at the antibody doses (0.75 and 0.5 mg/kg) and 211At activities (8.436–22.792 MBq; 0.228–0.616 mCi ...