Phase 1
N=16
Yttrium-90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk AML, ALL, or MDS
Chronic Myelomonocytic Leukemia · Previously Treated Myelodysplastic Syndrome · Recurrent Adult Acute Lymphoblastic Leukemia · Recurrent Adult Acute Myeloid Leukemia · Refractory Anemia With Excess Blasts
Bottom Line
View on ClinicalTrials.gov: NCT01300572 ↗Enrolled (actual)
16
Serious AEs
60.0%
Results posted
Jan 2019
Primary outcome: Primary: The MTD of Radiation Delivered Via 90Y-DOTA-BC8 When Combined With FLU and 2 Gy TBI as a Preparative Regimen for Patients Aged ≥ 18 With Advanced AML, ALL, and High-risk MDS. — 28 Gy
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Allogeneic Bone Marrow Transplantation (Procedure); Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Cyclosporine (Drug); Fludarabine Phosphate (Drug); Indium In 111 Anti-CD45 Monoclonal Antibody BC8 (Biological); Laboratory Biomarker Analysis (Other); Mycophenolate Mofetil (Drug); Peripheral Blood Stem Cell Transplantation (Procedure); Pharmacological Study (Other); Total-Body Irradiation (Radiation); Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Oct 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The MTD of Radiation Delivered Via 90Y-DOTA-BC8 When Combined With FLU and 2 Gy TBI as a Preparative Regimen for Patients Aged ≥ 18 With Advanced AML, ALL, and High-risk MDS. |
28 | — |
| SECONDARY Achievement of Remission |
13 | — |
| SECONDARY Disease-free Survival |
7 | — |
| SECONDARY Duration of Remission |
213 | — |
| SECONDARY Estimation of Absorbed Radiation Doses to Normal Organs, Marrow and Tumor |
11.4; 17.2; 3.1; 70 | — |
| SECONDARY Overall Survival |
7 | — |
| SECONDARY Rates of Acute GvHD |
4; 1; 6; 2; 1 | — |
| SECONDARY Rates of Donor Chimerism |
14 | — |
| SECONDARY Rates of Engraftment |
16 | — |
| SECONDARY Rates of Non-relapse Mortality |
1; 1 | — |
Summary
This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90 anti-cluster of differentiation 45 (CD45) monoclonal antibody BC8 (90Y-BC8) followed by donor stem cell transplant in treating patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) that is likely to come back or spread. Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body irradiation (TBI) before a donor peripheral blood stem cell (PBSC) or bone marrow transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies, such as 90Y-BC8, can find cancer cells and carry cancer-killing substances to them without harming normal 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 make an immune response against the body's normal cells. Giving FLU, 90Y-BC8, and TBI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
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; or
- MDS expressed as refractory anemia with excess blasts (RAEB) or 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 (serum creatinine value must be within 28 days prior to registration)
- Bilirubin = 70
- Patients must have an expected survival of > 60 days and must be free of active infection
- Patients must have an human leukocyte antigen (HLA)-identical sibling donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) or other donor center criteria for 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
- Doors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; 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 hematopoietic cell transplant (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 and 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
- DONOR: Donors must meet HLA matching criteria and standard SCCA and/or National Marrow Donor Program (NMDP) or other donor center criteria for PBSC or bone marrow donation
Exclusion Criteria
- Circulating human anti-mouse antibody (HAMA)
- Prior radiation to maximally tolerated levels to any critical normal organ, or > 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis)
- 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 diffusion lung capacity of carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen
- Liver abnormalities: fulminant liver failure, cirrhosis o
Data sourced from ClinicalTrials.gov (NCT01300572). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.