Trial record 8 of 81 for:    "Acute erythroleukemia" "Acute erythroid leukemia"

Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01427881
First received: August 31, 2011
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient's immune system from rejecting the donor's stem cells. Healthy stem cells from a donor that are infused into the patient help the patient's bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body's normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.


Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Myeloid Leukemia in Remission
Adult Erythroleukemia (M6a)
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Adult Pure Erythroid Leukemia (M6b)
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Erythroleukemia (M6)
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Megakaryocytic Leukemia (M7)
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Myelomonocytic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Philadelphia Chromosome Negative Chronic Myelogenous Leukemia
Post-transplant Lymphoproliferative Disorder
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage III Multiple Myeloma
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: cyclophosphamide
Drug: cyclosporine
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Drug: fludarabine phosphate
Drug: busulfan
Procedure: allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate the Efficacy of Posttransplant Cyclophosphamide for Prevention of Chronic Graft-versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Multiple Myeloma Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Homologous Wasting Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Peripheral T-cell Lymphoma Acute Erythroblastic Leukemia Acute Erythroid Leukemia Di Guglielmo's Syndrome Acute Megakaryoblastic Leukemia Chronic Graft Versus Host Disease Leukemia, T-cell, Chronic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Mycosis Fungoides Sezary Syndrome Chronic Myeloproliferative Disorders Myelodysplastic/myeloproliferative Disease
U.S. FDA Resources

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

Primary Outcome Measures:
  • Chronic GVHD requiring systemic immunosuppressive treatment [ Time Frame: At 1 year after transplantation ] [ Designated as safety issue: No ]
    Chronic GVHD will be defined by National Institutes of Health (NIH) criteria and requiring systemic treatment. A reduction in the cumulative incidence of GVHD from ~35% to ~15% at 1 year would represent a reasonable goal. A sample size of 42 patients provides 90% power to observe such a difference with one-side 5% type-1 error.


Secondary Outcome Measures:
  • Donor engraftment [ Time Frame: At day 28 ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to assess the mean and median proportions of donor myeloid cells and T cells in the blood. In addition, the proportions of patients with full and mixed chimerism will be summarized. Subsequent testing will be done as needed for clinical management. Mixed chimerism will be defined as > 5% and < 95% donor cells, and full chimerism is defined as at least 95% donor cells.

  • Grades II-IV and III-IV acute GVHD [ Time Frame: Through day +100 post-transplant ] [ Designated as safety issue: No ]
    Grades II-IV and III-IV GVHD will be assessed with the use of cumulative incidence plots.

  • Duration of systemic immunosuppressive treatment [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The need for additional immunosuppressive treatment with agents other than those used for prophylaxis, the reasons for their administration (acute GVHD, chronic GVHD, or other reasons) and the duration of its administration will be determined. Patients will be monitored to determine the duration of systemic immunosuppressive treatment. Primary and secondary treatment of acute GVHD and withdrawal of systemic immunosuppressive treatment will be assessed with the use of cumulative incidence plots.

  • Persistent or recurrent malignancy after HCT [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Recurrent or progressive malignancy will be assessed with the use of cumulative incidence plots. Recurrent malignancy will be defined by hematologic criteria. Recurrent malignancy will also be defined as any unplanned medical intervention designed to prevent progression of malignant disease in patients who have molecular, cytogenetic or flow-cytometric evidence of malignant cells after transplantation.

  • Non-relapse mortality [ Time Frame: Up to 1 year after transplant ] [ Designated as safety issue: No ]
    Defined as death in the absence of recurrent or progressive malignancy after HCT. Non-relapse morality will be assessed with the use of cumulative incidence plots. This secondary endpoint will be characterized and presented as a cumulative incidence.

  • Overall survival [ Time Frame: At 1 year after transplantation ] [ Designated as safety issue: No ]
    Overall survival will be evaluated as Kaplan-Meier estimates.

  • Disease-free survival [ Time Frame: At 1 year after transplantation ] [ Designated as safety issue: No ]
    Disease-free survival will be evaluated as Kaplan-Meier estimates.

  • Hematologic recovery [ Time Frame: Up to day +100 ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to assess the median days of neutrophil and platelet recovery. The day of neutrophil recovery is defined as the first day of three consecutive lab values on different days, after the conditioning regimen-induced nadir of blood counts, that the absolute neutrophil count is > 500/uL. The day of platelet recovery is defined as the first day of three consecutive lab values on different days, after the conditioning regimen-induced nadir of blood counts, that the platelet count is >= 20,000/uL without platelet transfusion support in the seven days prior.

  • Graft failure [ Time Frame: By greater than or equal to 28 days post-transplant ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to assess the incidence of primary graft failure and secondary graft failure. Primary graft failure is defined as failure to achieve a sustained neutrophil count of >= 500/uL by >= 28 days post-transplant. Secondary graft failure is defined as the decline in neutrophil count to < 500/uL after achieving engraftment which is unrelated to infection or drug effect and is unresponsive to stimulation by growth factors.


Estimated Enrollment: 42
Study Start Date: September 2011
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (TBI, PBSCT, and cyclophosphamide GVHD prophylaxis)

PREPARATIVE REGIMEN: Patients receive TBI BID on days -4 or -3 to -1. Some patients also receive fludarabine IV daily on days -5 to -2 and busulfan IV over 3 hours QD or over 2 hours every 6 hours on days -5 to -2. Patients may also undergo CNS prophylaxis, testicular irradiation, and/or involved field irradiation as per standard practice.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0 per standard practice.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4. Patients also receive cyclosporine IV every 12 hours or every 8 hours beginning on day 5 with taper on days 56-126.

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cyclosporine
Given IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSCT

Detailed Description:

PRIMARY OBJECTIVES:

I. The primary objective of this study is to assess outcomes when high-dose cyclophosphamide (CY) is administered on days 3 and 4 followed by cyclosporine (CSP) after human leukocyte antigen (HLA)-matched related or unrelated mobilized blood cell transplantation with total-body irradiation (TBI) or busulfan (BU)-based conditioning.

SECONDARY OBJECTIVES:

I. The secondary objective of this study is to assess hematopoietic cell transplantation (HCT) outcomes when withdrawal of CSP is accelerated in patients without acute graft-versus-host disease (GVHD).

OUTLINE: Patients' conditioning regimens are determined by the Clinical Coordinator after consultation with the attending physician. Based on disease, patients receive either TBI or fludarabine and busulfan.

PREPARATIVE REGIMEN: Patients receive TBI twice daily (BID) on days -4 or -3 to -1. Some patients also receive fludarabine intravenously (IV) daily on days -5 to -2 and busulfan IV over 3 hours once daily (QD) or over 2 hours every 6 hours on days -5 to -2. Patients may also undergo central nervous system (CNS) prophylaxis, testicular irradiation, and/or involved field irradiation as per standard practice.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0 per standard practice.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4. Patients also receive cyclosporine IV every 12 hours or every 8 hours beginning on day 5 with taper on days 56-126.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at day 180 and then annually for 5 years.

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute lymphocytic leukemia (ALL) in morphologic first complete remission (CR1) with high risk features defined as, but not limited to: evidence of adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) rearrangements; presence of minimal residual disease; progenitor B-cell immunophenotype; high white blood cells (WBC) at diagnosis (> 30,000/ul in B-ALL; > 100,000/ul in T-ALL); or delayed attainment of CR (> 4 weeks) after induction therapy; additional clinical characteristics deemed to confer a high relapse risk may be discussed with and approved by the Principal Investigator (PI)
  • Acute myeloid leukemia (AML) in CR1 EXCEPT patients with low-risk features defined as:

    • Inv 16 or t(8;21) in the absence of c-kit mutations
    • Normal karyotype who are FLT3-ITD-negative and NPM1-positive in the absence of c-kit mutations
    • Patients with respective "low-risk" features are eligible, however, if (i) more than 1 cycle of induction therapy was required to achieve CR1 (ii) the patient had a preceding myelodysplastic syndrome (MDS) other than myelofibrosis, or (iii) secondary AML
  • Acute leukemia in 2nd or greater CR (CR >= 2)
  • Refractory or relapsed AML with =< 10% bone marrow blasts and no circulating blasts or proven extramedullary disease
  • AML transformed from myelodysplastic syndrome (MDS) with < 10% bone marrow blasts
  • MDS with following high risk features:

    • High risk cytogenetics (including, but not limited to: 7q--, inv[3], t[3q], del[3q] or complex karyotype)
    • International Prognostic Scoring System (IPSS) intermediate (INT)-2 or greater
    • Treatment-related MDS
    • Any phase of MDS if patient is < 21 years of age
  • Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant or intolerant to tyrosine kinase inhibitors (adults) or any phase (pediatric < 21 years)
  • Chronic myelomonocytic leukemia
  • Philadelphia-negative myeloproliferative disorder
  • Lymphoma: relapsed chemotherapy-sensitive (complete or partial response) Hodgkin or non-Hodgkin lymphoma
  • Multiple myeloma-stage III
  • The patient or legal representative must be able to understand and give written informed consent
  • DONORS: The donor must be a genotypically HLA-identical sibling, a phenotypically HLA-matched first-degree relative, or an unrelated donor who is molecularly matched with the patient at HLA-A, B, C, DRB1
  • DONORS: Donors must meet the selection criteria for administration of G-CSF (filgrastim) and apheresis defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB)
  • DONORS: Donors must be capable of giving informed consent

Exclusion Criteria:

  • Prior autologous or allogeneic stem cell transplant
  • Performance status > 2 (Eastern Cooperative Oncology Group [ECOG]) or < 50 (Lansky; for patients < 16 years old)
  • Uncontrolled infection; the protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is under adequate control to allow enrollment in the study
  • Positive serology for human immunodeficiency virus (HIV)-1, 2 or human T cell lymphotropic virus (HTLV)-1, 2
  • Left ventricular ejection fraction < 45% or shortening fraction < 25%; no uncontrolled arrhythmias or symptomatic cardiac disease
  • Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =< 50% of predicted (corrected for hemoglobin); if pulmonary function tests cannot be performed, an oxygen saturation < 92% on room air
  • Calculated (Cockcroft-Gault or appropriate calculation for pediatric patients) serum creatinine clearance =< 60 mL/min; if the calculated CrCl is 50-60 mL/min, but a measured CrCl by 24 hour urine collection is > 60 mL/min, this measurement is acceptable
  • Total serum bilirubin more than twice upper normal limit
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3-fold higher than laboratory upper normal limits
  • Female patient must have negative serum pregnancy test (all women of child bearing-potential must have test performed)
  • DONORS: Potential donors who for psychological, physiological, or medical reasons cannot tolerate administration of G-CSF or apheresis
  • DONORS: Donors who are allergic to filgrastim or Escherichia (E.) coli-derived proteins
  • DONORS: Donor-related risks to recipients
  • DONORS: Positive anti-donor lymphocytotoxic crossmatch
  • DONORS: Donors who are positive for HIV
  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: NCT01427881

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Marco Mielcarek 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: NCT01427881     History of Changes
Other Study ID Numbers: 2541.00, NCI-2011-02459, P30CA015704
Study First Received: August 31, 2011
Last Updated: August 13, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Blast Crisis
Burkitt Lymphoma
Graft vs Host Disease
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Erythroblastic, Acute
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Megakaryoblastic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Chronic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell
Mycoses
Mycosis Fungoides
Myelodysplastic Syndromes

ClinicalTrials.gov processed this record on August 26, 2014