Clinical Trials /

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

NCT03670966

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Refractory Anemia with Excess Blasts
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 211At-BC8-B10 and Donor Stem Cell Transplant in Treating Relapsed or Refractory AML, ALL, 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 Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)

Clinical Trial IDs

  • ORG STUDY ID: RG1003349
  • SECONDARY ID: 10060
  • SECONDARY ID: 5P30CA015704
  • SECONDARY ID: NCI-2018-01788
  • NCT ID: NCT03670966

Conditions

  • 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

Interventions

DrugSynonymsArms
Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10At 211 MAb BC8-B10Treatment
Fludarabine2-Fluoro-9-beta-arabinofuranosyladenineTreatment
Cyclophosphamide(-)-CyclophosphamideTreatment
Tacrolimus109581-93-3, FK 506Treatment
Mycophenolate Mofetil115007-34-6, MMFTreatment
Sirolimus226080, RapamuneTreatment
Granulocyte Colony-Stimulating FactorColony Stimulating Factor 3, Granulocyte Colony Stimulating FactorTreatment

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalPREPARATIVE 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
  • Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
  • Fludarabine
  • Cyclophosphamide
  • Tacrolimus
  • Mycophenolate Mofetil
  • Sirolimus
  • Granulocyte Colony-Stimulating Factor

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity
Time Frame:Up 100 days after hematopoietic cell transplantation (HCT)
Safety Issue:
Description:Proportion of patients who develop grades III/IV Bearman regimen-related toxicity.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 100 days
Safety Issue:
Description:
Measure:Disease-free survival
Time Frame:Up to day 100
Safety Issue:
Description:
Measure:Number of patients experiencing Moderate/severe chronic GVHD
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Number of patients experiencing Immune reconstitution
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Non-relapse mortality (NRM)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Donor chimerism
Time Frame:At days 28, 56, 84, 180, and at 1 year
Safety Issue:
Description:
Measure:Rate of engraftment
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Achievement of remission
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Last Updated

October 1, 2019