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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


Phase 2
N/A
65 Years
Open (Enrolling)
Both
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

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Trial Information

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


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.


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])

- 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 beta-human chorionic gonadotrophin (beta-HCG)
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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Chronic GVHD requiring systemic immunosuppressive treatment

Outcome Description:

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.

Outcome Time Frame:

At 1 year after transplantation

Safety Issue:

No

Principal Investigator

Marco Mielcarek

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

2541.00

NCT ID:

NCT01427881

Start Date:

September 2011

Completion Date:

Related Keywords:

  • 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
  • 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, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Lymphoproliferative Disorders
  • Waldenstrom Macroglobulinemia
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Philadelphia Chromosome
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell
  • Hematologic Neoplasms

Name

Location
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109