Palifermin with Leuprolide Acetate or Degarelix after Total-Body Irradiation Based Donor Stem Cell Transplant in Treating Patients with Hematologic Malignancies
This phase II trial studies how well palifermin with leuprolide acetate or degarelix works after total body-irradiation based donor stem cell transplant in treating patients with hematologic malignancies. Giving chemotherapy and total body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving palifermin and leuprolide acetate or degarelix and removing the T cells from the donor cells before transplant may stop this from happening. It is not yet known whether giving palifermin with leuprolide acetate or degarelix is more effective in helping the immune system recover faster after a donor stem cell transplant.
- 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
Locations & Contacts
Contact: Christina Cho
Trial Objectives and Outline
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 & Type
Memorial Sloan Kettering Cancer Center
Secondary IDs NCI-2012-02983
Clinicaltrials.gov ID NCT01746849