Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00589316
First received: January 3, 2008
Last updated: October 10, 2014
Last verified: October 2014

January 3, 2008
October 10, 2014
October 2007
March 2015   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
A DLT will be defined as a grade III/IV (Bearman scale) toxicity that occurs within 30 days following transplant.
  • Maximum tolerated dose of iodine I 131 monoclonal antibody BC8 [ Designated as safety issue: Yes ]
  • Incidence of dose-limiting toxicities within the first 100 days after transplant [ Designated as safety issue: Yes ]
  • Rate of nonrelapse-related mortality [ Designated as safety issue: No ]
  • Rate of engraftment [ Designated as safety issue: No ]
  • Rate of donor chimerism [ Designated as safety issue: No ]
  • Incidence of acute graft-versus-host disease within the first 100 days after transplant [ Designated as safety issue: No ]
  • Achievement and duration of remission [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00589316 on ClinicalTrials.gov Archive Site
  • Rates of immune reconstitution [ Time Frame: Through day 100 ] [ Designated as safety issue: No ]
  • Rates of engraftment [ Time Frame: Through day 100 ] [ Designated as safety issue: No ]
  • Rates of donor chimerism [ Time Frame: Through day 100 ] [ Designated as safety issue: No ]
  • Rates of acute GVHD [ Time Frame: Through day 100 ] [ Designated as safety issue: Yes ]
    Graded according to the established criteria at the Fred Hutchinson Cancer Research Center.
  • Rates of disease-free survival [ Time Frame: Through day 100 ] [ Designated as safety issue: No ]
  • Rates of disease relapse [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Rate of immune reconstitution [ Designated as safety issue: No ]
  • Disease-free survival at 100 days [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

This phase II trial studies the side effects and best dose of iodine I 131monoclonal antibody BC8 when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation and donor bone marrow transplant and to see how well they work in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia that has spread to nearby or other places in the body (advanced), or high-risk myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor 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. 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 cyclophosphamide together with mycophenolate mofetil and tacrolimus after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, fludarabine phosphate, cyclophosphamide, mycophenolate mofetil and tacrolimus may be an effective treatment for advanced acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes.

PRIMARY OBJECTIVES:

I. To determine 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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • 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)
  • Chronic Myelomonocytic Leukemia
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Ringed Sideroblasts
  • Refractory Cytopenia With Multilineage Dysplasia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • Fludara
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Radiation: total-body irradiation
    Undergo TBI
    Other Name: TBI
  • Radiation: iodine I 131 monoclonal antibody BC8
    Given IV (dosimetry dose) or via central line (therapeutic dose)
    Other Names:
    • I 131 MOAB BC8
    • I 131 Monoclonal Antibody BC8
    • iodine I 131 MOAB BC8
  • Procedure: allogeneic bone marrow transplantation
    Given via central line
    Other Names:
    • bone marrow therapy, allogeneic
    • bone marrow therapy, allogenic
    • transplantation, allogeneic bone marrow
    • transplantation, allogenic bone marrow
  • Drug: tacrolimus
    Given IV or PO
    Other Names:
    • FK 506
    • Prograf
  • Drug: mycophenolate mofetil
    Given IV or PO
    Other Names:
    • Cellcept
    • MMF
  • Other: laboratory biomarker analysis
    Correlative studies
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.

Interventions:
  • Drug: fludarabine phosphate
  • Drug: cyclophosphamide
  • Radiation: total-body irradiation
  • Radiation: iodine I 131 monoclonal antibody BC8
  • Procedure: allogeneic bone marrow transplantation
  • Drug: tacrolimus
  • Drug: mycophenolate mofetil
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
Not Provided
March 2015   (final data collection date for primary outcome measure)

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)
  • 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 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
Both
18 Years and older
No
United States
 
NCT00589316
2186.00, NCI-2010-00404, 2186.00, P01CA044991, P30CA015704
No
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Johnnie Orozco Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP