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