211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome

  • STATUS
    Recruiting
  • End date
    Sep 1, 2024
  • participants needed
    30
  • sponsor
    Fred Hutchinson Cancer Center
Updated on 16 May 2022
cancer
remission
sirolimus
stem cell transplantation
graft versus host disease
total body irradiation
fludarabine
tacrolimus
anemia
mycophenolate mofetil
cyclophosphamide
hla-a
bone marrow transplant
hydroxyurea
acute leukemia
white blood cell count
chronic myelomonocytic leukemia
monoclonal antibodies
granulocyte colony stimulating factor
cell transplantation
leukemia
myeloproliferative syndromes
blast cells
colony stimulating factor
g-csf
wbc count
myelomonocytic leukemia
nucleated cells
mycophenolate
hla matching
nucleated cell count
anti-cd45 monoclonal antibody bc8
leukemic blasts

Summary

This phase I/II trial studies the side effects and best dose of a radioactive agent linked to an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after a transplant may stop this from happening.

Description

OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody BC8-B10.

PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine intravenously (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 peripheral blood stem cell (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 three times daily (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 granulocyte colony-stimulating factor (G-CSF) IV or subcutaneously (SC) on day 5 to continue until absolute neutrophil count (ANC) > 1000/mm^3 x 3 days.

After completion of study treatment, patients are followed up at day 100, and at 6, 9, 12, 18, and 24 months.

Details
Condition 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, Refractory Acute Myeloid Leukemia, Recurrent Mixed Phenotype Acute Leukemia, Refractory Mixed Phenotype Acute Leukemia, Hematopoietic and Lymphoid Cell Neoplasm
Treatment cyclophosphamide, fludarabine phosphate, mycophenolate mofetil, peripheral blood stem cell transplantation, Fludarabine, Tacrolimus, Total-Body Irradiation, Sirolimus, Bone Marrow Transplantation, Granulocyte colony-stimulating factor, Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10, Recombinant Granulocyte Colony-Stimulating Factor
Clinical Study IdentifierNCT03670966
SponsorFred Hutchinson Cancer Center
Last Modified on16 May 2022

Eligibility

Yes No Not Sure

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 beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)
AML, ALL, or MPAL in first remission with evidence of measurable residual disease (MRD) by flow cytometry
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 should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed)
Patients not in remission must have CD45-expressing leukemic blasts. Patients in
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
remission do not require phenotyping and may have leukemia previously
Bilirubin < 2 times the upper limit of normal
documented to be CD45 negative (because in remission patients, virtually all
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the upper limit of normal
antibody binding is to non-malignant cells which make up >= 95% of nucleated
cells in the marrow)
Eastern Cooperative Oncology Group (ECOG) < 2 or Karnofsky >= 70
Patients must be free of uncontrolled infection
Patients must not have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or bone marrow donation
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
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
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
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
Patients with prior myeloablative allogeneic-HCT
Inability to understand or give an informed consent
Allergy to murine-based monoclonal antibodies
Known contraindications to radiotherapy
Clear my responses

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