Radioimmunotherapy + Stem Cell Transplant for Leukemia and Myelodysplastic Syndrome

Overseen By Phuong Vo

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: Unknown

30 Participants Needed

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 safety of a new treatment for certain blood cancers, such as leukemia or myelodysplastic syndrome, that resist standard treatments. The treatment combines a special radioactive agent attached to an antibody (Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10) with a donor stem cell transplant. It targets cancer cells while aiding the recovery of the patient's bone marrow with healthy cells. This trial suits individuals with conditions like acute leukemia or high-risk myelodysplastic syndrome, particularly if their disease has returned or not responded to other treatments. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this innovative therapy.

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, it mentions that controlling blast count with hydroxyurea or a similar agent is allowed, which suggests some medications might be continued. It's best to discuss your specific medications with the trial team.

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

Research has shown that the treatment using the monoclonal antibody 211At-BC8-B10 is generally safe. Early studies found that 43% of patients treated with this antibody survived for at least one year, suggesting it merits further investigation. It has been used alongside other treatments and is usually well-tolerated.

Cyclophosphamide, a common cancer treatment, has a well-established safety record. Research indicates it can lower the risk of graft-versus-host disease, a condition where donor cells attack the recipient's body, when used after a stem cell transplant. This makes it a good option for managing side effects in these procedures.

Both treatments are still under study to fully understand their safety, but early results are encouraging. Participants should always discuss potential risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines radioimmunotherapy with a stem cell transplant, potentially offering a powerful new approach for leukemia and myelodysplastic syndrome. Unlike traditional treatments that typically rely on chemotherapy alone, this treatment uses astatine At 211, a radioactive element, attached to a monoclonal antibody targeting CD45, a protein found on the surface of leukemia cells. This targeted approach allows for direct delivery of radiation to cancer cells, potentially increasing effectiveness while minimizing damage to healthy tissue. Additionally, combining this with a stem cell transplant could improve patient outcomes by restoring healthy blood-forming cells. This innovative combination offers hope for more effective and less toxic treatment options.

What evidence suggests that this trial's treatments could be effective for leukemia and myelodysplastic syndrome?

Research has shown that the 211At-BC8-B10 treatment, which participants in this trial will receive, could effectively fight leukemia and myelodysplastic syndrome. In earlier studies, 43% of patients survived for at least a year, and 35% remained cancer-free during that time. This suggests the treatment might stop cancer cells from growing and spreading. Cyclophosphamide, another part of the trial, already treats similar cancers and can help prevent graft-versus-host disease, where transplanted cells attack the body. Both treatments have shown promising results in managing these conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Phuong Vo

Principal Investigator

Fred Hutchinson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with high-risk acute leukemia or myelodysplastic syndrome that's recurrent or refractory. Eligible patients must have certain types of leukemia, adequate organ function, and no uncontrolled infections. They can't have an HLA-matched donor available, severe heart/liver conditions, active HIV/CNS leukemia, be pregnant/breastfeeding, or unable to consent.

Inclusion Criteria

I had a specific type of stem cell transplant and meet certain conditions.

I can take care of myself and perform daily activities without help.

Bilirubin < 2 times the upper limit of normal

Exclusion Criteria

My lung function is severely reduced or I need extra oxygen.

I am currently pregnant or breastfeeding.

Left ventricular ejection fraction < 45%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion, fludarabine, and cyclophosphamide, and undergo total body irradiation (TBI)

8 days

Transplant

Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant

1 day

GVHD Prophylaxis

Patients receive cyclophosphamide, mycophenolate mofetil, and tacrolimus to prevent graft versus host disease, and begin granulocyte colony-stimulating factor (G-CSF)

Up to 180 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
• Cyclophosphamide
• Mycophenolate Mofetil
• Tacrolimus

Trial Overview The trial tests a radioactive antibody (211At-BC8-B10) followed by a stem cell transplant from a donor to treat high-risk blood cancers. It includes chemotherapy and total body irradiation to prepare the bone marrow for new cells and medications post-transplant to prevent graft versus host disease.

How Is the Trial Designed?

Group I: Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) Experimental Treatment 11 Interventions

PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine IV over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Patients also undergo TBI on day -1. TRANSPLANT: Patients undergo PBSC or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or PO TID on days 5-35, and tacrolimus IV over 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per physician discretion. Patients also begin G-CSF IV or SC on day 5 to continue until ANC \> 1000/mm\^3 x 3 days. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the 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+

Published Research Related to This Trial

In a phase 1/2 study involving 59 patients with acute myeloid leukemia, the combination of targeted irradiation using 131I-anti-CD45 antibody with busulfan and cyclophosphamide showed promising results, with 61% disease-free survival at 3 years.

The treatment was well tolerated, and the estimated nonrelapse mortality was 21%, suggesting that adding targeted irradiation may improve outcomes compared to conventional therapies alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Pagel, JM., Appelbaum, FR., Eary, JF., et al.[2021]

Astatine-211 ((211)At) showed superior effectiveness in inducing myelosuppression and myeloablation compared to bismuth-213 ((213)Bi), with lethal myeloablation occurring in all mice receiving higher doses of (211)At, while (213)Bi did not produce similar effects at the same doses.

(211)At demonstrated a better safety profile, causing no renal toxicity and less severe nonhematologic toxicity compared to (213)Bi, which resulted in acute hepatic toxicity at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistributions, myelosuppression, and toxicities in mice treated with an anti-CD45 antibody labeled with the alpha-emitting radionuclides bismuth-213 or astatine-211. Nakamae, H., Wilbur, DS., Hamlin, DK., et al.[2021]

In a study involving 25 patients with high-risk relapsed/refractory leukemia or myelodysplastic syndrome, the use of iodine-131 (131I)-anti-CD45 radioimmunotherapy combined with nonmyeloablative conditioning before haploidentical hematopoietic cell transplantation (HCT) resulted in a 100% morphologic remission rate within 28 days post-transplant.

The treatment showed promising long-term outcomes, with 1-year overall survival and progression-free survival rates of 40% and 32%, respectively, indicating that this approach can be curative for some patients without adding significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Radiation Delivery Before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-Term Survivors. Orozco, JJ., Vo, PT., Gooley, TA., et al.[2023]

In a study of 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), the use of rhenium 188-labeled anti-CD66 monoclonal antibody as part of the conditioning regimen before stem cell transplantation provided a significant additional radiation dose to the marrow (mean 15.3 Gy) with minimal infusion-related toxicity and no increase in treatment-related mortality.

The treatment showed promising outcomes with low early mortality rates (3% at day +30 and 6% at day +100) and a 20% relapse rate for patients undergoing transplantation in complete remission, indicating that this intensified conditioning regimen is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study. Bunjes, D., Buchmann, I., Duncker, C., et al.[2021]

In a pilot study involving 30 pediatric and adolescent patients, targeted irradiation using a ⁹⁰Y-labeled anti-CD66 monoclonal antibody effectively achieved myeloablation while maintaining low systemic toxicity, especially when combined with reduced-intensity conditioning.

The study showed promising survival rates, with 2-year overall survival probabilities of 69% for patients with malignant disorders and 94% for those with nonmalignant disorders, indicating the potential efficacy of radioimmunotherapy in treating these young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases. Schulz, AS., Glatting, G., Hoenig, M., et al.[2021]

High-dose radioimmunotherapy (RIT) using a modified CD66b-specific monoclonal antibody showed promising results in patients with acute myeloid leukemia and other blood cancers, with 4 out of 5 patients achieving complete remission three months after treatment.

The treatment was well tolerated with no acute adverse events related to RIT, indicating a favorable safety profile, although two patients experienced delayed liver failure unrelated to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of Radiolabeling of a [90Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation. Winter, G., Hamp-Goldstein, C., Fischer, G., et al.[2023]

In a study involving 31 patients with relapsed or refractory acute myeloid leukemia and other conditions, combining iodine-131 labeled monoclonal antibodies targeting CD33 with busulfan and cyclophosphamide as conditioning for bone marrow transplantation was found to be feasible, with targeted radiation effectively reaching the bone marrow, liver, and spleen.

The treatment resulted in a median survival of 4.9 months, with three patients achieving long-term remission of over 59 months, indicating potential efficacy, though further randomized trials are necessary to confirm the benefits of this intensified conditioning approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias. Burke, JM., Caron, PC., Papadopoulos, EB., et al.[2013]

In a study of 57 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), the use of a 188Re-labeled anti-CD66 monoclonal antibody as part of the conditioning regimen before stem cell transplantation provided a significant additional radiation dose to the marrow, enhancing treatment efficacy with minimal toxicity.

The treatment resulted in a 64% disease-free survival rate for patients with low blast counts (< 15% blasts in the marrow at transplant), while those with higher blast counts had only an 8% disease-free survival, indicating the importance of disease status at the time of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

188Re-labeled anti-CD66 monoclonal antibody in stem cell transplantation for patients with high-risk acute myeloid leukemia. Bunjes, D.[2019]

Radiolabeled monoclonal antibodies targeting the CD45 antigen can deliver significantly more radiation to lymph nodes and bone marrow compared to other organs, potentially reducing relapse rates in leukemia patients after bone marrow transplantation.

The study found that the higher avidity AC8 antibody, when administered at a higher dose, resulted in better uptake in lymph nodes, suggesting that optimizing antibody dosage could enhance the effectiveness of radiation therapy in treating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque. Matthews, DC., Appelbaum, FR., Eary, JF., et al.[2021]

Astatine-211 (211At) radioimmunotherapy (RIT) targeting the CD123 antigen shows promising results in selectively killing acute leukemia and myelodysplastic syndrome (MDS) cells, including neoplastic stem cells, in mouse models.

In immunodeficient mice, a single dose of 211At-labeled anti-CD123 monoclonal antibodies significantly reduced tumor burdens and improved survival in CD123+ leukemia, demonstrating its potential efficacy and specificity for treating these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [211At]astatine-based anti-CD123 radioimmunotherapy for acute leukemias and other CD123+ malignancies. Laszlo, GS., Orozco, JJ., Kehret, AR., et al.[2023]

Citations

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

Astatine-211 BC8-B10 for Leukaemia Astatine-211 BC8-B10, targeting CD45 in leukaemia, combines monoclonal antibodies with Astatine-211, showing promising clinical potential.

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

211 At-Labeled Anti-CD45 Antibody as a ... Twelve of the 17 dogs survived over 30 d, with donor chimerism ranging from 3% to 99%. Conclusion: The results suggest that nonmyeloablative ...

3. 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 ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/astatine-at-211-anti-cd45-monoclonal-antibody-bc8-b10?pn=1

Clinical Trials Using Astatine At 211 Anti-CD45 Monoclonal ... Review the clinical trials studying astatine at 211 anti-cd45 monoclonal antibody bc8-b10 on this list and use the filters to refine the results by age and ...

5. 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 ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03128034/

Clinical Trial: NCT03128034 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 ...

7. researchgate.net researchgate.net/publication/348921967_A_Phase_I_Trial_of_First-in-Human_Alpha-Emitter_Astatine-211-Labeled_Anti-CD45_Antibody_211At-BC8-B10_in_Combination_with_Fludarabine_and_TBI_As_Conditioning_for_Allogeneic_Hematopoietic_Cell_Transpla

A Phase I Trial of First-in-Human Alpha-Emitter Astatine- ... A Phase I Trial of First-in-Human Alpha-Emitter Astatine-211-Labeled Anti-CD45 Antibody (211At-BC8-B10) in Combination with Fludarabine and ...