211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia

  • STATUS
    Recruiting
  • End date
    Mar 22, 2025
  • participants needed
    50
  • sponsor
    Fred Hutchinson Cancer Center
Updated on 7 October 2022
cancer
remission
sirolimus
stem cell transplantation
myeloid leukemia
lymphoid leukemia
total body irradiation
fludarabine
anemia
mycophenolate mofetil
hla-a
cyclosporine
hydroxyurea
acute leukemia
flow cytometry
chronic myelomonocytic leukemia
monoclonal antibodies
cell transplantation
leukemia
lymphocytic leukemia
myeloproliferative syndromes
residual tumor
blast cells
myelomonocytic leukemia
mycophenolate
leukemia, acute lymphoblastic
nucleated cell count
leukemic blasts

Summary

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 acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.

Description

OUTLINE: This is a dose-escalation study of 211^At-BC8-B10.

Patients receive 211^At-BC8-B10 intravenously (IV) over 6-8 hours on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and peripheral blood stem cell (PBSC) transplant on day 0. Patients also receive cyclosporine orally (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, or every 8 hours on day 0 and then reduced to every 12 hours on days 30-40. Patients with HLA-matched unrelated donors receive sirolimus PO once daily (QD) on days -3 to 150 and then tapered to day 180.

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

Details
Condition Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome With Excess Blasts, Recurrent Acute Myeloid Leukemia, Refractory Acute Lymphoblastic Leukemia, Recurrent Acute Lymphoblastic Leukemia, Recurrent Mixed Phenotype Acute Leukemia, Refractory Acute Myeloid Leukemia, Refractory Mixed Phenotype Acute Leukemia, Mixed Phenotype Acute Leukemia
Treatment cyclosporine, fludarabine phosphate, mycophenolate mofetil, laboratory biomarker analysis, peripheral blood stem cell transplantation, Fludarabine, Total-Body Irradiation, Sirolimus, pharmacological study, Pretargeted Radioimmunotherapy
Clinical Study IdentifierNCT03128034
SponsorFred Hutchinson Cancer Center
Last Modified on7 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients must have advanced 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 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
documented to be CD45 negative (because in remission patients, virtually all
Patients must have normal hepatic function (bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] < 2 times the upper limit of normal)
Eastern Cooperative Oncology Group (ECOG) < 2 or Karnofsky >= 70
antibody binding is to non-malignant cells which make up >= 95% of nucleated
Patients must be free of uncontrolled infection
cells in the marrow)
Patients must have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or bone marrow donation, as follows
Related donor: related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed by high-resolution typing
Patients with prior non-myeloablative or reduced-intensity conditioning allogeneic-hematopoietic cell transplant (HCT) must have no evidence of ongoing GVHD and be off all immunosuppression for at least 6 weeks at time of enrollment
Unrelated donor
Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR
Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
Patient and donor pairs homozygous at a mismatched allele in the graft rejection
vector are considered a two-allele mismatch, i.e., the patient is A _0101 and
the donor is A_ 0102, and this type of mismatch is not allowed

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 < 35%
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
Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen; when pulmonary function test (PFT)s 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
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 positive [beta-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
Patients with prior myeloablative allogeneic-HCT
Allergy to murine-based monoclonal antibodies
Known contraindications to radiotherapy
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note