Overview

This trial is active, not recruiting.

Conditions adult acute myeloid leukemia with 11q23 (mll) abnormalities, adult acute myeloid leukemia with del(5q), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), childhood myelodysplastic syndromes, chronic myelomonocytic leukemia, previously treated myelodysplastic syndromes, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes
Treatments iodine i 131 monoclonal antibody bc8, fludarabine phosphate, total-body irradiation, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, cyclosporine, mycophenolate mofetil, laboratory biomarker analysis
Phase phase 2
Sponsor Fred Hutchinson Cancer Research Center
Collaborator National Cancer Institute (NCI)
Start date May 2003
End date August 2014
Trial size 15 participants
Trial identifier NCT00119366, 1809.00, NCI-2010-00234, P30CA015704

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
RADIOIMMUNOTHERAPY: 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.
iodine i 131 monoclonal antibody bc8 I 131 MOAB BC8
Given IV
fludarabine phosphate 2-F-ara-AMP
Given IV
total-body irradiation TBI
Undergo TBI
allogeneic hematopoietic stem cell transplantation
Undergo PBSC transplantation
peripheral blood stem cell transplantation PBPC transplantation
Undergo PBSC transplantation
cyclosporine ciclosporin
Given IV or PO
mycophenolate mofetil Cellcept
Given PO
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
Incidence of dose-limiting toxicities to determine MTD of radiation delivered to normal organ by iodine I 131 monoclonal antibody BC8
time frame: Up to 100 days post-transplant

Secondary Outcomes

Measure
Rates of transplant-related mortality for patients receiving iodine I 131 monoclonal antibody BC8 when combined with 2 Gy TBI + CSP/MMF
time frame: Up to 100 days post-transplant
Disease response in patients receiving iodine I 131 monoclonal antibody BC8 combined with fludarabine phosphate, 2 Gy TBI, CSP, MMR and HLA-matched related or unrelated allogeneic HSCT
time frame: Up to 11 years
Disease-free survival in patients receiving iodine I 131 monoclonal antibody BC8 combined with fludarabine phosphate, 2 Gy TBI, CSP, MMR and HLA-matched related or unrelated allogeneic HSCT
time frame: Up to 2 years
Rates of donor chimerism and graft-versus-host disease
time frame: Days 28, 56, and 84

Eligibility Criteria

Male or female participants from 16 years up to 50 years old.

Inclusion Criteria: - 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 Exclusion Criteria: - 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

Additional Information

Official title 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
Principal investigator Johnnie Orozco
Description PRIMARY OBJECTIVES: I. To evaluate the maximum tolerated dose (MTD) and the transplant-related mortality (TRM) and toxicity of delivering 131I-BC8 (iodine I 131 monoclonal antibody BC8) (anti-cluster of differentiation [CD]45 antibody) at a starting dose of 22 Gy to the normal organ receiving the highest dose in combination with the non-myeloablative regimen of fludarabine (fludarabine phosphate) (FLU), 2 Gy total body irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and human leukocyte antigen (HLA)-matched related or unrelated allogeneic hematopoietic stem cell transplant (HSCT) in patients 16 to 50 years old who have advanced acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS). II. To estimate rates of donor chimerism resulting from this combined preparative regimen and to correlate level of donor chimerism with estimated radiation doses delivered to hematopoietic tissues via antibody. III. To determine rates of disease relapse, graft vs. host disease, and 2-year disease-free survival in patients receiving 131I-BC8 antibody combined with FLU, 2 Gy TBI, CSP, MMF, and HLA-matched related or unrelated allogeneic HSCT. OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8. RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 intravenously (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 peripheral blood stem cell (PBSC) transplant on day 0. IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or orally (PO) twice daily (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 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 thrice daily (TID) on days 0 to 40 followed by a taper to day 96. After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months and then annually thereafter.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.