Study Stopped
Funding ended before target accrual was reached; participants are no longer being examined or receiving intervention.
Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome
A Phase II Trial Combining Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine and Low Dose TBI Followed by Related or Unrelated PBSC Infusion and Post-Transplant Immunosuppression for Patients With Advanced AML or High Risk Myelodysplastic Syndrome
3 other identifiers
interventional
18
1 country
1
Brief Summary
This phase II trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine phosphate, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has spread to other places in the body and usually cannot be cured or controlled with treatment. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell 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. Also, radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 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 fludarabine phosphate and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, cyclosporine, and mycophenolate mofetil may be an effective treatment for advanced acute myeloid leukemia or myelodysplastic syndromes.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started May 2003
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2003
CompletedFirst Submitted
Initial submission to the registry
July 12, 2005
CompletedFirst Posted
Study publicly available on registry
July 13, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 8, 2019
CompletedResults Posted
Study results publicly available
August 1, 2022
CompletedDecember 12, 2022
December 1, 2022
11.3 years
July 12, 2005
March 29, 2022
December 9, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Dose-limiting Toxicities (DLT) 100 Days After Transplant
The criteria of Grade III/IV regimen-related toxicity (Bearman) or dose-limiting toxicity (DLT) are as follows: Grade 1 Development of transient chemical abnormalities which are not of major clinical consequence and which reverse without requiring major medical interventions. In general, the intent of this toxicity scale is to observe transient target organ toxicity which is reversible. Grade 2 Development of chemical or laboratory abnormalities that are persistent and which may represent target organ damage that may not be readily reversed. It is anticipated that at this dose of the drug, the toxicity obtained would be manageable by clinical methods but may interfere with other therapies. Grade 3 Development of major clinical, chemical or laboratory abnormalities which represent maximum toxicities without being fatal. This grade of toxicity is designed to be the dose-limiting toxicity.
Up to 100 days post-transplant
Secondary Outcomes (5)
Number of Participants With Transplant Related Mortality Within 100 Days After Transplant
Up to 100 days post-transplant
Participant Disease Response Within 4 Weeks After Transplant
4 weeks after transplant
Severity of Acute GVHD in Patients Who Completed the Study Treatment
100 days after transplant
Number of Participants With 100% Donor Chimerism at Day 28 and Day 84
Day 28 and Day 80 after transplant
Two-year Disease-free Survival of Study Participants Who Completed the Study Regimen
2 years post transplant
Study Arms (5)
Dose Level 1: 12 Gy iodine-131 monoclonal antibody BC8
EXPERIMENTALRADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 IV on day -12. CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: After completion of TBI, patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or PO BID on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO 2 BID on days 0 to 27. Patients with a matched unrelated donor receive cyclosporine IV or PO BID on days -3 to 100 followed by a taper to day 180. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO TID on days 0 to 40 followed by a taper to day 96.
Dose Level 7: 22 Gy iodine-131 monoclonal antibody BC8
EXPERIMENTALRADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 IV on day -12. CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: After completion of TBI, patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or PO BID on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO 2 BID on days 0 to 27. Patients with a matched unrelated donor receive cyclosporine IV or PO BID on days -3 to 100 followed by a taper to day 180. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO TID on days 0 to 40 followed by a taper to day 96.
Dose Level 8: 24 Gy iodine-131 monoclonal antibody BC8
EXPERIMENTALRADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 IV on day -12. CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: After completion of TBI, patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or PO BID on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO 2 BID on days 0 to 27. Patients with a matched unrelated donor receive cyclosporine IV or PO BID on days -3 to 100 followed by a taper to day 180. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO TID on days 0 to 40 followed by a taper to day 96.
Dose Level 9: 26 Gy iodine-131 monoclonal antibody BC8
EXPERIMENTALRADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 IV on day -12. CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: After completion of TBI, patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or PO BID on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO 2 BID on days 0 to 27. Patients with a matched unrelated donor receive cyclosporine IV or PO BID on days -3 to 100 followed by a taper to day 180. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO TID on days 0 to 40 followed by a taper to day 96.
Dose Level 10: 28 Gy iodine-131 monoclonal antibody BC8
EXPERIMENTALRADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 IV on day -12. CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: After completion of TBI, patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or PO BID on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO 2 BID on days 0 to 27. Patients with a matched unrelated donor receive cyclosporine IV or PO BID on days -3 to 100 followed by a taper to day 180. Beginning 4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO TID on days 0 to 40 followed by a taper to day 96.
Interventions
Given IV
Given IV
Undergo TBI
Undergo PBSC transplantation
Undergo PBSC transplantation
Given IV or PO
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients with advanced AML defined as beyond first remission, primary refractory disease, or evolved from myelodysplastic or myeloproliferative syndromes; or patients with MDS expressed as refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEBT), refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)
- Patients not in remission must have CD45-expressing leukemic blasts or myelodysplastic cells; 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 \< 2 times the upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2 times the upper limit of normal
- Karnofsky score \>= 70 or Eastern Cooperative Oncology Group (ECOG) =\< 2
- Patients must have an expected survival of \> 60 days and must be free of active infection
- Patients must have an 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 peripheral blood stem cell (PBSC) donation; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and developmentally regulated RNA binding protein 1 (DRB1) according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQB1; unrelated donors should be identified using matching criteria that follows the FHCRC Standard Practice Guidelines limiting the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1 (grade 1), and accepting up to one allele mismatch as per Standard Practice grade 2.1 for HLA-A, B, or C
- DONOR: Donors must meet HLA matching criteria as well as standard SCCA and/or NMDP or other donor center criteria for PBSC donation
You may not qualify if:
- Circulating antibody against mouse immunoglobulin (human anti-mouse antibody \[HAMA\])
- Prior radiation to maximally tolerated levels to any normal organ
- Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects
- Inability to understand or give an informed consent
- Patients who are seropositive for human immunodeficiency virus (HIV)
- Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
- Patients who have previously undergone autologous or allogeneic HSCT
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Early termination leading to small numbers of subjects analyzed
Results Point of Contact
- Title
- Johnnie Orozco, MD, PhD
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Johnnie Orozco
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 12, 2005
First Posted
July 13, 2005
Study Start
May 1, 2003
Primary Completion
August 1, 2014
Study Completion
May 8, 2019
Last Updated
December 12, 2022
Results First Posted
August 1, 2022
Record last verified: 2022-12