Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome
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| ClinicalTrials.gov Identifier: NCT00589316 |
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Recruitment Status :
Active, not recruiting
First Posted : January 9, 2008
Last Update Posted : September 22, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission CD45-Positive Neoplastic Cells Present Chronic Myelomonocytic Leukemia Previously Treated Myelodysplastic Syndrome Refractory Anemia With Excess Blasts Refractory Anemia With Ring Sideroblasts Refractory Cytopenia With Multilineage Dysplasia Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts | Procedure: Allogeneic Bone Marrow Transplantation Drug: Cyclophosphamide Drug: Fludarabine Phosphate Radiation: Iodine I 131 Monoclonal Antibody BC8 Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Drug: Tacrolimus Radiation: Total-Body Irradiation | Phase 1 |
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose of radiation delivered via 131 I-BC8 antibody (iodine I 131 monoclonal antibody BC8) when combined with pre- and post-transplant cyclophosphamide (CY), fludarabine phosphate (FLU), 2 Gy total-body irradiation (TBI), tacrolimus, mycophenolate mofetil (MMF), and a haploidentical allogeneic hematopoietic marrow transplant in patients who have advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS).
II. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting from this combined preparative regimen.
III. To determine rates of disease relapse, acute graft-versus-host disease (GVHD), and day 100 disease-free survival in patients receiving 131 I-BC8 antibody (Ab) combined with CY, FLU, 2 Gy TBI, tacrolimus, MMF, and human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic cell transplant (HCT).
OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.
RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 via central line on day -14.
NONMYELOABLATIVE CONDITIONING: Patients receive FLU intravenously (IV) over 30 minutes on days -6 to -2 and CY IV over 1 hour on days -6 and -5. Patients undergo TBI on day -1.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
POST-TRANSPLATATION IMMUNOSUPPRESSION: Patients receive CY IV over 1-2 hours on day 3, MMF IV or orally (PO) thrice daily (TID) on days 4 to 35, and tacrolimus IV over 1-2 hours or PO on days 4 to 180 with taper on day 84.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months, and then annually thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 26 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Hematopoietic Bone Marrow Transplantation for Patients With High-risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Related HLA-Mismatched Donors: A Trial Using Radiolabeled Anti-CD45 Antibody Combined With Immunosuppression Before and After Transplantation |
| Actual Study Start Date : | October 5, 2007 |
| Actual Primary Completion Date : | October 1, 2016 |
| Estimated Study Completion Date : | October 1, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (chemo, TBI, transplant, immunosuppression)
RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 via central line on day -14. NONMYELOABLATIVE CONDITIONING: Patients receive FLU IV over 30 minutes on days -6 to -2 and CY IV over 1 hour on days -6 and -5. Patients undergo TBI on day -1. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0. POST-TRANSPLATATION IMMUNOSUPPRESSION: Patients receive CY IV over 1-2 hours on day 3, MMF IV or PO TID on days 4 to 35, and tacrolimus IV over 1-2 hours or PO on days 4 to 180 with taper on day 84. |
Procedure: Allogeneic Bone Marrow Transplantation
Given via central line
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Radiation: Iodine I 131 Monoclonal Antibody BC8 Given IV (dosimetry dose) or via central line (therapeutic dose)
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mycophenolate Mofetil Given IV or PO
Other Names:
Drug: Tacrolimus Given IV or PO
Other Names:
Radiation: Total-Body Irradiation Undergo TBI
Other Names:
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- Maximum tolerated dose of 131 I-BC8 antibody defined as the dose that is associated with a true dose limiting toxicity (DLT) rate of 25%, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3 [ Time Frame: Up to 30 days post-transplant ]A DLT will be defined as a grade III/IV (Bearman scale) toxicity that occurs within 30 days following transplant.
- Disease-free survival [ Time Frame: Up to 8 years ]
- Overall survival [ Time Frame: Up to 8 years ]
- Rates of acute GVHD [ Time Frame: Through day 100 ]Graded according to the established criteria at the Fred Hutchinson Cancer Research Center.
- Rates of disease relapse [ Time Frame: Up to 8 years ]
- Rates of disease-free survival [ Time Frame: Through day 100 ]
- Rates of donor chimerism [ Time Frame: Through day 100 ]
- Rates of engraftment [ Time Frame: Through day 100 ]
- Rates of immune reconstitution [ Time Frame: Through day 100 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with advanced AML or ALL 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 cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)
- Patients not in remission must have cluster of differentiation (CD)45-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)
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Patients must have a creatinine clearance greater than 50/ml per minute by the following formula (test must be performed within 28 days prior to registration):
- Creatinine clearance (CrCl) = (140-age) (Wt in Kg) x 0.85 (female) OR 1.0 (male)/72 x serum Cr
- 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 a related donor who is identical for one human leukocyte antigen (HLA) haplotype and mismatched at the HLA-A, -B or class II, DR beta 1 (DRB1) loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches
- DONOR: 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
Exclusion Criteria:
- Circulating antibody against mouse immunoglobulin (HAMA)
- Prior radiation to maximally tolerated levels to any critical normal organ
- Cross-match positive with donor
- 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 capacity of carbon monoxide (DLCO) < 35% and/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 seropositive for human immunodeficiency virus (HIV)
- Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
- Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy and/or standard cranial-spinal radiotherapy
- Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin positive [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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00589316
| United States, Washington | |
| Fred Hutch/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: | Johnnie Orozco | Fred Hutch/University of Washington Cancer Consortium |
| Responsible Party: | Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00589316 |
| Other Study ID Numbers: |
2186.00 NCI-2010-00404 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2186.00p 2186.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) P01CA044991 ( U.S. NIH Grant/Contract ) P30CA015704 ( U.S. NIH Grant/Contract ) RG1707019 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) |
| First Posted: | January 9, 2008 Key Record Dates |
| Last Update Posted: | September 22, 2020 |
| Last Verified: | September 2020 |
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Anemia Myelodysplastic Syndromes Anemia, Refractory Anemia, Refractory, with Excess of Blasts Leukopenia Thrombocytopenia Syndrome |
Disease Pathologic Processes Neoplasms by Histologic Type Neoplasms Hematologic Diseases Bone Marrow Diseases Precancerous Conditions Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Myelodysplastic-Myeloproliferative Diseases Leukocyte Disorders Blood Platelet Disorders Iodine |