Astatine-211 for Acute Myeloid Leukemia

Overseen By Brenda M. Sandmaier

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Cardiac medications

Disqualifiers: Coronary artery disease, HIV, others

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

Compensation: Varies

Number of Visits: 100

Duration: Approximately 8 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using a radioactive substance, astatine-211, to target and kill cancer cells in patients with high-risk blood cancers like acute myeloid leukemia. The goal is to determine the optimal dose and understand any side effects before a stem cell transplant. The treatment links the radioactive material to antibodies that specifically bind to cancer cells, aiming to spare healthy cells. This trial may suit those with these specific types of leukemia or related conditions who have not responded to other therapies. Participants should have an HLA-matched donor for the stem cell transplant. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 treatment is likely to be safe for humans?

Research has shown that the treatment 211^At-BC8-B10 is being tested for safety before donor stem cell transplants in patients with certain types of leukemia. Earlier studies suggest this treatment may effectively target cancer cells while sparing healthy ones.

The main goal is to determine the best dose of this treatment. So far, patients have generally tolerated it well, but since it's still under study, some side effects might not be fully known yet. This trial is in its early stages, so safety is being closely monitored, and more information is needed to understand any risks.

It's important to remember that this treatment is still under investigation, so anyone considering joining the trial should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Astatine-211 for Acute Myeloid Leukemia because it introduces a new approach with its radioimmunotherapy mechanism. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, Astatine-211 is part of a targeted therapy that uses a radioactive isotope, 211^At, linked to a monoclonal antibody, BC8-B10. This combination allows it to directly target and destroy leukemia cells with precision, potentially minimizing damage to healthy cells. This targeted method could lead to fewer side effects and improved outcomes for patients compared to the existing standards of care like chemotherapy and allogeneic stem cell transplantation.

What evidence suggests that 211^At-BC8-B10 might be an effective treatment for acute myeloid leukemia?

In this trial, participants will receive a treatment called 211^At-BC8-B10, which may offer promise for individuals with high-risk acute myeloid leukemia (AML). This treatment uses a radioactive substance, astatine-211, attached to antibodies that specifically target cancer cells. In a previous study, 43% of patients survived after one year, and 35% experienced no cancer recurrence. These findings suggest that 211^At-BC8-B10 can effectively attack and destroy cancer cells while sparing healthy cells. Given the serious nature of AML, these results are encouraging and support further research. ^{1 2 3 4 6}

Who Is on the Research Team?

Brenda M. Sandmaier

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with high-risk leukemias or myelodysplastic syndromes who have relapsed after remission, are not responding to treatments, or have disease evolved from other blood disorders. They must have low levels of leukemia cells in the blood and normal kidney and liver function. It's not suitable for those in first remission without measurable residual disease.

Inclusion Criteria

I am mostly active and can care for myself.

Patients should have a circulating blast count of less than 10,000/mm^3

Patients must have normal elastography

Exclusion Criteria

Patients who are known to be seropositive for human immunodeficiency virus (HIV)

I have had a bone marrow transplant from a donor.

Perceived inability to tolerate diagnostic or therapeutic procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 211^At-BC8-B10 IV, potentially 131^I-BC8-B10 IV, fludarabine phosphate IV, undergo TBI and PBSC transplant, and receive cyclosporine and mycophenolate mofetil

Approximately 8 weeks

Multiple visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including SPECT, bone marrow aspirate, and blood sample collection

Up to 24 months

Follow-up visits at 100 days, 6, 9, 12, 18, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• 211^At-BC8-B10

Trial Overview The trial tests a radioactive drug (211^At-BC8-B10) given before a stem cell transplant from a donor. The goal is to see how well it works at killing cancer cells while sparing healthy ones, determining the best dose and assessing side effects.

How Is the Trial Designed?

Group I: Treatment (211^At-BC8-B10, PBSC) Experimental Treatment 8 Interventions

Patients receive 211\^At-BC8-B10 IV over 6-8 hours on day -7 and may receive 131\^I-BC8-B10 IV on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and PBSC transplant on day 0. Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 and then tapered to day 180, or continuing to day 96 and then tapered to day 150. Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6 hours after PBSC infusion) every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on day 0 and then reduced to every 12 hours on days 30-150 then tapered to day 180 (for patients with unrelated donors). Patients may undergo SPECT, bone marrow aspirate sample and blood sample collection on study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. 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 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521692621000852

Effectiveness of allogeneic hematopoietic cell ... In 2021, an estimated 20,240 patients in the United States were diagnosed with acute myeloid leukemia (AML). Their projected 5-year survival is 29% and is very ...

3. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_11939.211-at-bc8-b10-before-donor-stem-cell-transplant-in-treating-patients-with-high-risk-acute-myeloid-leukemia-acute-lymphoblastic-leukemia-or.html

211^At-BC8-B10 Before Donor Stem Cell Transplant in ... This phase I/II trial studies the side effects and best dose of 211^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk ...

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

cGMP production of astatine-211-labeled anti-CD45 ... Stability of 211At-BC8-B10​​ The results shown in Table 3 indicate the radiochemical purity of the 211At-BC8-B10 remains above 95% after being ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-00452

211^At-BC8-B10 before Donor Stem Cell Transplant in ... This phase I/II trial studies the side effects and best dose of 211^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk ...

6. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_12681.211at-bc8-b10-and-donor-stem-cell-transplant-in-treating-relapsed-or-refractory-aml-all-or-myelodysplastic-syndrome.html

211At-BC8-B10 and Donor Stem Cell Transplant in ... Monoclonal antibodies, such as 211At-BC8-B10, may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation ...