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211At-BC8-B10 and Donor Stem Cell Transplant in Treating Relapsed or Refractory AML, ALL, or Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT03670966
Recruitment Status : Recruiting
First Posted : September 14, 2018
Last Update Posted : October 3, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

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 participants with acute myeloid leukemia, or acute lymphoblastic leukemia, or myelodysplastic syndrome that has come back or isn't responding to treatment. Monoclonal antibodies, such as 211At-BC8-B10, 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 participant, they may help the participant'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, tacrolimus, mycophenolate mofetil, and sirolimus after a transplant may stop this from happening.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Acute Myeloid Leukemia in Remission CD45-Positive Neoplastic Cells Present Chronic Myelomonocytic Leukemia High Risk Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts Myeloproliferative Neoplasm Recurrent Acute Lymphoblastic Leukemia Recurrent Acute Myeloid Leukemia Refractory Acute Lymphoblastic Leukemia Refractory Acute Myeloid Leukemia Biological: Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10 Drug: Fludarabine Drug: Cyclophosphamide Radiation: Total-Body Irradiation Procedure: Peripheral Blood Stem Cell Transplantation Procedure: Bone Marrow Transplantation Drug: Tacrolimus Drug: Mycophenolate Mofetil Drug: Sirolimus Biological: Granulocyte Colony-Stimulating Factor Phase 1 Phase 2

Detailed Description:

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

PREPARATIVE REGIMEN: Participants receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion 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. Participants also undergo TBI on day -1.

TRANSPLANT: Participants undergo PBSC or bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Participants receive cyclophosphamide IV over 1-2 hours on days 3-4, tacrolimus IV over 1-2 hours or orally (PO) on days 5-150 with a taper beginning on day 84, mycophenolate mofetil IV or PO on days 5-35, and sirolimus PO daily on days 5-180 with taper beginning on day 150. Participants 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, participants are followed up at day 100, and at 6, 9, 12, 18, and 24 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)
Actual Study Start Date : March 20, 2019
Estimated Primary Completion Date : September 1, 2023
Estimated Study Completion Date : September 1, 2024


Arm Intervention/treatment
Experimental: Treatment

PREPARATIVE REGIMEN: Participants receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion day -8, fludarabine IV over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Participants also undergo Total-Body Irradiation on day -1.

TRANSPLANT: Participants undergo Peripheral Blood Stem Cell Transplantation or Bone Marrow Transplantation day 0.

GVHD PROPHYLAXIS: Participants receive cyclophosphamide IV over 1-2 hours on days 3-4, tacrolimus IV over 1-2 hours or PO on days 5-150 with a taper beginning on day 84, mycophenolate mofetil IV or PO on days 5-35, and sirolimus PO daily on days 5-180 with taper beginning on day 150. Participants also begin Granulocyte Colony-Stimulating Factor IV or SC on day 5 to continue until ANC > 1000/mm^3 X 3 days

Biological: Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
Given via infusion
Other Name: At 211 MAb BC8-B10

Drug: Fludarabine
Given IV
Other Name: 2-Fluoro-9-beta-arabinofuranosyladenine

Drug: Cyclophosphamide
Given IV
Other Name: (-)-Cyclophosphamide

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • TBI
  • Whole Body Irradiation
  • Whole-Body Irradiation

Procedure: Peripheral Blood Stem Cell Transplantation
Undergo PBSC transplantation
Other Name: PBPC transplantation

Procedure: Bone Marrow Transplantation
Undergo bone marrow transplant
Other Names:
  • Bone Marrow Grafting
  • BMT

Drug: Tacrolimus
Given IV or PO
Other Names:
  • 109581-93-3
  • FK 506

Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • 115007-34-6
  • MMF

Drug: Sirolimus
Given PO
Other Names:
  • 226080
  • Rapamune

Biological: Granulocyte Colony-Stimulating Factor
Given IV or SC
Other Names:
  • Colony Stimulating Factor 3
  • Granulocyte Colony Stimulating Factor




Primary Outcome Measures :
  1. Toxicity [ Time Frame: Up 100 days after hematopoietic cell transplantation (HCT) ]
    Proportion of patients who develop grades III/IV Bearman regimen-related toxicity.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 100 days ]
  2. Disease-free survival [ Time Frame: Up to day 100 ]
  3. Number of patients experiencing Moderate/severe chronic GVHD [ Time Frame: Up to 2 years ]
  4. Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD) [ Time Frame: Up to 2 years ]
  5. Number of patients experiencing Immune reconstitution [ Time Frame: Up to 2 years ]
  6. Non-relapse mortality (NRM) [ Time Frame: Up to 2 years ]
  7. Donor chimerism [ Time Frame: At days 28, 56, 84, 180, and at 1 year ]
  8. Rate of engraftment [ Time Frame: Up to 2 years ]
  9. Achievement of remission [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:

    • AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen);
    • AML or ALL 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 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 SCCA or NMDP or other donor center 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.
  • 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.
  • Inability to understand or give an informed consent.
  • Allergy to murine-based monoclonal antibodies.
  • Known contraindications to radiotherapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03670966


Contacts
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Contact: Phuong Vo 206-667-2749 ptvo@fredhutch.org

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Phuong Vo         
Principal Investigator: Phuong Vo         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Phuong Vo Fred Hutchinson Cancer Research Center

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Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03670966     History of Changes
Other Study ID Numbers: RG1003349
10060 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
5P30CA015704 ( U.S. NIH Grant/Contract )
NCI-2018-01788 ( Registry Identifier: NCI / CTRP )
First Posted: September 14, 2018    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Myeloproliferative Disorders
Anemia, Refractory, with Excess of Blasts
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myelodysplastic-Myeloproliferative Diseases
Anemia, Refractory
Anemia
Sirolimus
Mycophenolic Acid
Cyclophosphamide
Fludarabine