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

Primary Purpose

Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia in Remission

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
Cyclophosphamide
Total-Body Irradiation
Peripheral Blood Stem Cell Transplantation
Bone Marrow Transplantation
Mycophenolate Mofetil
Recombinant Granulocyte Colony-Stimulating Factor
Fludarabine Phosphate
Tacrolimus
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia in Remission focused on measuring Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Other Hematopoietic

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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 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.
  • 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.

Sites / Locations

  • Fred Hutch/University of Washington Cancer ConsortiumRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Arm Description

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.

Outcomes

Primary Outcome Measures

Toxicity: Proportion of patients who develop grades III/IV Bearman regimen-related toxicity
Proportion of patients who develop grades III/IV Bearman regimen-related toxicity.

Secondary Outcome Measures

Achievement of remission
Rate of engraftment
Donor chimerism
Non-relapse mortality (NRM)
Number of patients experiencing Immune reconstitution
Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD)
Number of patients experiencing Moderate/severe chronic GVHD
Overall survival
Disease-free survival

Full Information

First Posted
September 12, 2018
Last Updated
June 9, 2023
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03670966
Brief Title
211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2019 (Actual)
Primary Completion Date
January 17, 2024 (Anticipated)
Study Completion Date
October 9, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Other Hematopoietic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
Other Intervention Name(s)
At 211 MAb BC8-B10, APAMISTAMAB-B10-ASTATINE AT-211
Intervention Description
Given via infusion
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Total-Body Irradiation
Other Intervention Name(s)
Total Body Irradiation, SCT_TBI, Whole Body Irradiation, Whole-Body Irradiation, TBI
Intervention Description
Undergo TBI
Intervention Type
Procedure
Intervention Name(s)
Peripheral Blood Stem Cell Transplantation
Other Intervention Name(s)
PBPC transplantation
Intervention Description
Undergo PBSC transplantation
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Transplantation
Other Intervention Name(s)
Bone Marrow Grafting, BMT
Intervention Description
Undergo bone marrow transplant
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
115007-34-6, MMF
Intervention Description
Given IV or PO
Intervention Type
Biological
Intervention Name(s)
Recombinant Granulocyte Colony-Stimulating Factor
Other Intervention Name(s)
143011-72-7, Recombinant Colony-Stimulating Factor 3, rhG-CSF
Intervention Description
Given IV or SC
Intervention Type
Drug
Intervention Name(s)
Fludarabine Phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara, Fludarabine-5''-Monophosphate, SH T 586
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Prograf, Protopic
Intervention Description
Given IV or PO
Primary Outcome Measure Information:
Title
Toxicity: Proportion of patients who develop grades III/IV Bearman regimen-related toxicity
Description
Proportion of patients who develop grades III/IV Bearman regimen-related toxicity.
Time Frame
Up 100 days after hematopoietic cell transplantation (HCT)
Secondary Outcome Measure Information:
Title
Achievement of remission
Time Frame
Up to 2 years
Title
Rate of engraftment
Time Frame
Up to 2 years
Title
Donor chimerism
Time Frame
At days 28, 56, 84, 180, and at 1 year
Title
Non-relapse mortality (NRM)
Time Frame
Up to 2 years
Title
Number of patients experiencing Immune reconstitution
Time Frame
Up to 2 years
Title
Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD)
Time Frame
Up to 2 years
Title
Number of patients experiencing Moderate/severe chronic GVHD
Time Frame
Up to 2 years
Title
Overall survival
Time Frame
Up to 100 days
Title
Disease-free survival
Time Frame
Up to day 100

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Phuong Vo
Phone
206-667-2749
Email
ptvo@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phuong Vo
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phuong Vo
Phone
206-667-2749
Email
ptvo@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Phuong Vo

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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