Using a radioactive antibody followed by stem cell transplant to treat high-risk leukemia or myelodysplastic syndrome

A Phase I/II Study Evaluating Escalating Doses of 211At-Labeled Anti-CD45 MAb BC8-B10 (211At-BC8-B10) Followed by Related Haplo-Identical Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Leukemia or Myelodysplastic Syndrome (MDS)

This study is testing a new radioactive treatment combined with a stem cell transplant to see if it can help people with high-risk leukemia or myelodysplastic syndrome feel better and improve their chances of recovery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fred Hutchinson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT03670966 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and optimal dosage of a radioactive monoclonal antibody (211At-BC8-B10) in patients with relapsed or refractory high-risk acute leukemia or myelodysplastic syndrome. The treatment involves administering the antibody, followed by chemotherapy and total body irradiation to prepare for a donor stem cell transplant. The goal is to enhance the effectiveness of the transplant by targeting cancer cells while supporting the recovery of healthy blood-forming cells. Patients will be monitored for side effects and treatment efficacy throughout the process.

Who should consider this trial

Good fit: Ideal candidates include patients with relapsed or refractory acute leukemia or myelodysplastic syndrome who have measurable residual disease or have not achieved remission after previous treatments.

Not a fit: Patients with low-risk leukemia or those who are not eligible for stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with high-risk leukemia or myelodysplastic syndrome.

How similar studies have performed: Other studies using monoclonal antibodies in combination with stem cell transplants have shown promise, but this specific approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Patients must have AML, ALL, high-risk MDS, or MPAL (also known as biphenotypic) meeting one of the following descriptions:

  * AML, ALL, or MPAL in first remission with evidence of measurable residual disease (MRD) by flow cytometry;
  * AML, ALL, or MPAL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen);
  * AML, ALL, or MPAL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens);
  * AML evolved from myelodysplastic or myeloproliferative syndromes;
  * MDS expressed as refractory anemia with excess blasts (RAEB)
  * Chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria.
* Patients not in remission must have CD45-expressing leukemic blasts. Patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up \>= 95% of nucleated cells in the marrow).
* Patients must be \>= 18 and =\< 75 years of age.
* Patients should have a circulating blast count of less than 10,000/mm\^3 (control with hydroxyurea or similar agent is allowed).
* Patients must have an estimated creatinine clearance greater than 50/ml per minute by the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 days prior to registration.
* Bilirubin \< 2 times the upper limit of normal.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2 times the upper limit of normal.
* Eastern Cooperative Oncology Group (ECOG) \< 2 or Karnofsky \>= 70.
* Patients must be free of uncontrolled infection.
* Patients with prior non-myeloablative or reduced-intensity conditioning allogeneic-HCT must have no evidence of ongoing GVHD and be off all immunosuppression for at least 6 weeks at time of enrollment.
* Patients must have normal elastography.
* If ferritin is elevated, patient must have less than 7 mg/g liver iron concentration on liver T2 magnetic resonance imaging (MRI).
* Patients should have an official gastrointestinal (GI) consult prior to the transplant for full evaluation.
* Patients must have a related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches.
* DONOR: Donors must meet HLA matching criteria as well as standard Seattle Cancer Care Alliance (SCCA) criteria for PBSC or bone marrow donation. Preference should be given to donors who are mismatched at the HLA-A, -B and -DRB1 loci.

Exclusion Criteria:

* Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects.
* Left ventricular ejection fraction \< 45%.
* Corrected diffusion capacity of the lung for carbon monoxide (DLCO) \< 35% or receiving supplemental continuous oxygen. When pulmonary function tests (PFTs) cannot be obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of \< 89% during a 6MWT will be excluded
* Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.
* Patients who are known to be seropositive for human immunodeficiency virus (HIV).
* Perceived inability to tolerate diagnostic or therapeutic procedures.
* Active central nervous system (CNS) leukemia at time of treatment.
* Patients with prior myeloablative allogeneic-HCT.
* Women of childbearing potential who are pregnant (beta human chorionic gonadotropin \[B-HCG\]+) or breast feeding.
* Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant.
* Inability to understand or give an informed consent.
* Allergy to murine-based monoclonal antibodies.
* Known contraindications to radiotherapy.

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Phuong Vo — Fred Hutchinson Cancer Center
• Study coordinator: Phuong Vo

Conditions Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Excess Blasts; Recurrent Acute Lymphoblastic Leukemia; Recurrent Acute Myeloid Leukemia; Refractory Acute Lymphoblastic Leukemia