Acute Lymphoblastic LeukemiaPhase 1/2NCT03128034

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

A Phase 1/2 study testing Cyclosporine, Fludarabine Phosphate and Mycophenolate Mofetil in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia
What is being tested?: Cyclosporine, Fludarabine Phosphate and Mycophenolate Mofetil
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 75 participants
Where: 1 siteUnited States
Study dates: 24 Oct 2017to 31 Mar 2029
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Show all 25Show fewer

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
Patients must have normal hepatic function (bilirubin within normal limits, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] < 2 times the upper limit of normal) within 2 months prior to the astatine-211 infusion date (with the exception of patients that are known to have Gilbert's disease, for whom total bilirubin is allowed up to 3 x upper limit of normal [ULN])
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-hematopoietic cell transplant (HCT) must have no evidence of ongoing GVHD and be off GVHD treatment 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* MRI
Patients should have an official gastrointestinal (GI) consult prior to the transplant for full evaluation
Patients must have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Fred Hutch 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
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

Who cannot join

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%
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
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

Show all 13Show fewer

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 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
Allergy to murine-based monoclonal antibodies
Known contraindications to radiotherapy

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Brenda M. Sandmaier contact

206-667-4961

bsandmai@fredhutch.org

United States1 site, 1 recruiting

Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Brenda M. Sandmaier, 206-667-4961, bsandmai@fredhutch.org
Brenda M. Sandmaier
Recruiting

Other trials in United States

About this study

Official title: A Study Evaluating Escalating Doses of 211^At-Labeled Anti-CD45 MAb BC8-B10 (211^At-BC8-B10) Followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)

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.

Read the detailed 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 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 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 (for patients with related donors), or continuing to day 96 and then tapered to day 150 (for patients with unrelated donors). 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 single photon emission computed tomography (SPECT), bone marrow aspirate sample and blood sample collection on study.

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

Conditions: 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
Being tested: Cyclosporine, Fludarabine Phosphate, Mycophenolate Mofetil, Peripheral Blood Stem Cell Transplantation, Pretargeted Radioimmunotherapy
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, with Excess of Blasts, Leukemia, Biphenotypic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CyclosporineDrug
Also called 27-400, Ciclosporin, CsA, Cyclosporin
Given PO or IV
Fludarabine PhosphateDrug
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Mycophenolate MofetilDrug
Also called Cellcept, MMF
Given PO or IV
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support
Undergo allogeneic PBSC transplant
Pretargeted RadioimmunotherapyRadiation
Given 211^At-BC8-B10 IV
Total-Body IrradiationRadiation
Also called Total Body Irradiation, Whole-Body Irradiation, TBI, Whole Body Irradiation
Undergo TBI
Pretargeted RadioimmunotherapyRadiation
Given 131^I-BC8-B10 IV
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection
Undergo blood and bone marrow aspirate sample collection
Single Photon Emission Computed TomographyProcedure or surgery
Also called SPECT, SPECT SCAN, Medical Imaging
Undergo SPECT

Study groups in NCT03128034
Study group	Role	What they receive
Treatment (211^At-BC8-B10, PBSC)	Experimental	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. Receives: Drug: Cyclosporine; Drug: Fludarabine Phosphate; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Pretargeted Radioimmunotherapy; Radiation: Total-Body Irradiation; Procedure: Biospecimen Collection; Procedure: Single Photon Emission Computed Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of dose limiting toxicity (DLT)
DLT is defined as a grade III/IV regimen-related toxicity (Bearman scale). The maximum tolerated dose will be defined as the dose of 211^At-BC8-B10 used in combination with the reduced-intensity hematopoietic cell transplantation conditioning regimen that is associated with a grade III/IV regimen-related toxicity or true DLT rate of 25%. The data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels visited. Based on this fitted model, the maximum tolerated dose is estimated to be the dose that is associated with a toxicity rate of 25%.
Measured: Up to 30 days post-transplant, with a review period for occurrence of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) extended to 60 days post-transplant

Secondary outcomes (8)

Engraftment
Sufficient evidence will be taken to be a lower limit of the appropriate 80% one-sided confidence interval associated with the estimated proportion of rejections in excess of 0.20.
Measured: Up to day 100
Chimerism
Measured: Up to day 84
Non-relapse mortality
Measured: Up to 2 years
Acute graft versus host disease
Measured: Up to day 180
Achievement of remission
Measured: Up to 2 years
Duration of remission
Measured: Up to 2 years
Overall survival
Measured: Up to 100 days
Disease-free survival
Measured: Up to 100 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Oct 201731 Mar 2029

First posted25 Apr 2017
Study start24 Oct 2017
Primary completion30 Jun 2027 (estimated)
Study completion31 Mar 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 75 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03128034
Sponsor's protocol ID: 9595
Other IDs: NCI-2017-00452, 9595, P01CA078902, RG9217014
Status last verified: Jun 2026
First submitted: 13 Apr 2017
Last updated: 22 Jun 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Li Y, Hamlin DK, Chyan MK, Wong R, Dorman EF, Emery RC, Woodle DR, Manger RL, Nartea M, Kenoyer AL, Orozco JJ, Green DJ, Press OW, Storb R, Sandmaier BM, Wilbur DS. cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. PLoS One. 2018 Oct 18;13(10):e0205135. doi: 10.1371/journal.pone.0205135. eCollection 2018.
PubMed 30335787