Palifermin with Leuprolide Acetate or Degarelix after Total-Body Irradiation Based Donor Stem Cell Transplant in Treating Patients with Hematologic Malignancies
- Patients must meet one of the following: * Acute myeloid leukemia (AML) in first (1st) remission - for patients whose AML does not have "good risk" cytogenetic features (i.e. t[8;21], t[15;17], inv 16 without v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [c-kit] mutations) * Acute leukemias of ambiguous lineage in >= 1st remission * Secondary AML in remission * AML in >= second (2nd) remission * Acute lymphoblastic leukemia (ALL) in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL >= 2nd remission * Chronic myelogenous leukemia (CML) failing to respond or not tolerating imatinib, dasatinib or nilotinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in complete remission (CR) after accelerated phase or blast crisis * Non-Hodgkin lymphoma (NHL) with chemo responsive disease in any of the following categories: ** Intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants ** Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant * Myelodysplastic syndrome (MDS): refractory anemia (RA)/refractory cytopenia with multilineage dysplasia (RCMD) with high risk cytogenetic features or transfusion dependence, refractory anemia with excess blasts (RAEB)-1 and RAEB-2 * Chronic myelomonocytic leukemia (CMML): CMML-1 and CMML-2
- Patients must have a Karnofsky (adult) or Lansky (pediatric) performance status >= 70%
- Cardiac: asymptomatic or if symptomatic then left ventricular ejection fraction (LVEF) at rest must be > 50% and must improve with exercise
- Pulmonary: asymptomatic or if symptomatic, diffusing capacity of the lung for carbon monoxide (DLCO) > 60% of predicted (corrected for hemoglobin)
- Hepatic: < 3 x upper limit of normal (ULN) alanine aminotransferase (ALT)
- Hepatic: < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
- Renal: serum creatinine < 1.2 mg/dl or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 50 ml/min (measured or calculated/estimated)
- Patients must have a plan to receive a CD34-selected peripheral blood stem cell transplant with TBI-based conditioning
- DONOR: Must be willing and able to undergo peripheral blood stem cell (PBSC) collection
- Active extramedullary disease
- Active and uncontrolled infection at the time of transplantation
- Patients who have undergone a prior allogeneic or autologous stem cell transplantation within the previous six months
- Pregnant or breast feeding
- Human immunodeficiency virus (HIV) infection
- Patient is felt not to be a candidate for total-body irradiation (TBI) by the Bone Marrow Transplant (BMT) service
I. To determine the percentage of patients who achieve a cluster of differentiation (CD)4+ T cell count of greater than 200 at 6 months as this endpoint has been associated with a decreased incidence of opportunistic infections (OIs).
I. Overall survival at 2 years.
II. Transplant related mortality at 6 months.
III. CD4+ T cell count at 12 months.
IV. Incidence of infections.
V. Relapse at 12 months.
VI. The incidence and severity of acute graft-versus-host disease (GVHD) at 100 days post allograft.
VII. Rates of non-engraftment.
VIII. Mucositis endpoints: grade, patient controlled anesthesia (PCA) use, total parenteral nutrition (TPN) use, length of transplant hospital stay (LOS).
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Beginning 2-6 weeks prior to pre-transplant conditioning regimen, patients receive leuprolide acetate intramuscularly (IM) and 3 months after the first dose. Patients receive palifermin intravenously (IV) on days -13 to -11 and 0-2, undergo total body irradiation (TBI) on days -9 to -6, and receive thiotepa IV over 2-4 hours on days -5 to -4, cyclophosphamide IV over 30-60 minutes on days -3 to -2, and anti-thymocyte globulin infused over 12 hours on days -3 to -2. Patients then undergo T-cell depleted allogeneic hematopoietic stem cell transplant on day 0. Patients also receive filgrastim subcutaneously (SC) once daily (QD) from day 7 until absolute neutrophil count (ANC) is > 2000 for 3 consecutive days.
ARM II: Beginning 4-14 days prior to pre-transplant conditioning regimen, patients receive degarelix SC. Beginning 1 month after the initial loading dose, patients receive degarelix SC every 28 days for up to 5 maintenance doses. Patients receive palifermin IV on days -13 to -11 and 0-2, undergo TBI on days -9 to -6, and receive thiotepa IV over 2-4 hours on days -5 to -4, cyclophosphamide IV over 30-60 minutes on days -3 to -2, and anti-thymocyte globulin infused over 12 hours on days -3 to -2. Patients then undergo T-cell depleted allogeneic hematopoietic stem cell transplant on day 0. Patients also receive filgrastim SC QD from day 7 until ANC is > 2000 for 3 consecutive days.
After completion of study treatment, patients are followed up once or twice weekly for 3 months, then every 4-6 weeks for 3 months, and then every 3-6 months for 2 years.
Trial Phase Phase II
Trial Type Supportive care
Memorial Sloan Kettering Cancer Center
- Primary ID 12-077
- Secondary IDs NCI-2012-02983
- Clinicaltrials.gov ID NCT01746849