Overview

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

Status:
Completed
Trial end date:
2015-07-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Fred Hutchinson Cancer Research Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Busulfan
Cyclophosphamide
Cyclosporine
Cyclosporins
Fludarabine
Fludarabine phosphate
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