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 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.
Title
- 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)
Clinical Trial IDs
- ORG STUDY ID:
RG1003349
- SECONDARY ID:
10060
- SECONDARY ID:
P30CA015704
- SECONDARY ID:
NCI-2018-01788
- SECONDARY ID:
P01CA078902
- NCT ID:
NCT03670966
Conditions
- 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
Interventions
Drug | Synonyms | Arms |
---|
Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10 | At 211 MAb BC8-B10 | Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) |
Cyclophosphamide | (-)-Cyclophosphamide | Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) |
Mycophenolate Mofetil | 115007-34-6, MMF | Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) |
Recombinant Granulocyte Colony-Stimulating Factor | 143011-72-7, Recombinant Colony-Stimulating Factor 3, rhG-CSF | Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) |
Fludarabine Phosphate | 2-F-ara-AMP, Beneflur, Fludara, Fludarabine-5''-Monophosphate, SH T 586 | Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) |
Tacrolimus | Prograf, Protopic | Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) |
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 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF) | Experimental | 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. | - Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
- Cyclophosphamide
- Mycophenolate Mofetil
- Recombinant Granulocyte Colony-Stimulating Factor
- Fludarabine Phosphate
- Tacrolimus
|
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 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.
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Toxicity: Proportion of patients who develop grades III/IV Bearman regimen-related 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: | Achievement of remission |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | |
Measure: | Rate of engraftment |
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: | Non-relapse mortality (NRM) |
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: | 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 Moderate/severe chronic GVHD |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | |
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: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Fred Hutchinson Cancer Research Center |
Trial Keywords
- Lymphoid Leukemia
- Myeloid and Monocytic Leukemia
- Other Hematopoietic
Last Updated
August 16, 2021