Trial record 2 of 410 for:    Open Studies | "Myelodysplastic Syndromes"

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 April 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: April 28, 2014
Last verified: April 2014
  Purpose

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 advanced acute myeloid leukemia, acute lymphoblastic leukemia, 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.


Condition Intervention Phase
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
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) 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 (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 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.


Secondary Outcome Measures:
  • 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 (FHCRC).

  • 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 ]

Estimated Enrollment: 50
Study Start Date: October 2007
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of radiation delivered via 131 I-BC8 antibody (iodine I 131monoclonal 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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589316

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: John M. Pagel    206-667-1868      
Principal Investigator: John M. Pagel         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: John Pagel Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00589316     History of Changes
Other Study ID Numbers: 2186.00, NCI-2010-00404, 2186.00, P30CA015704, P01CA044991
Study First Received: January 3, 2008
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Congenital Abnormalities
Anemia
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Acute
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myelodysplastic-Myeloproliferative Diseases
Precancerous Conditions
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cyclophosphamide
Mycophenolate mofetil
Fludarabine phosphate
Tacrolimus

ClinicalTrials.gov processed this record on August 28, 2014