Clinical trial NCT01532635
Conditions: Hematologic Malignancy Leukemia Acute Lymphoblastic Leukemia ALL Acute Myelogenous Leukemia AML Chronic Lymphocytic Leukemia CLL Lymphoma Hodgkin's Lymphoma Non-hodgkin's Lymphoma Myeloma
Keywords: hematologic malignancy leukemia Acute lymphoblastic leukemia ALL Acute myelogenous leukemia AML Chronic lymphocytic leukemia CLL lymphoma hodgkin's lymphoma non-hodgkin's lymphoma myeloma allogeneic stem cell transplant TJU 2-step Hematopoietic stem cell transplant HSCT bone marrow transplant Cyclophosphamide MMF Mycophenolate Mofetil
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
Start date: 2012-03-01; Completion date: 2013-05-01
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II clinical trial studies how well two donors stem cell transplant work in treating patients with high-risk hematologic malignancies. After receiving radiation to help further treat the disease, patients receive a dose of donors' T cells. T cells can fight infection and react against cancer cells. Two days after donors' T cells are given, patients receive cyclophosphamide (CY) to help destroy the most active T cells that may cause tissue damage (called graft versus host disease or GVHD). Some of the less reactive T cells are not destroyed by CY and they remain in the patient to help fight infection. A few days after the CY is given, patients receive donors' stem cells to help their blood counts recover. Using two donors' stem cell transplant instead of one donor may be more effective in treating patients with high-risk disease and may prevent the disease from coming back.

Detailed description:
PRIMARY OBJECTIVES:

I. To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach using 2 donors.

SECONDARY OBJECTIVES:

I. To assess the consistency and pace of engraftment. II. To assess the pace of T cell and B cell immune recovery in patients in each arm.

III. To assess regimen related toxicity, graft-versus-host disease (GVHD) incidence and severity, and overall survival.

IV. To assess the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups.

V. To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment.

VI. If dominance is observed, to compare the donors with regard to degree of human leukocyte antigen (HLA) mismatch, killer Ig-like receptor (KIR) types, cluster of differentiation (CD)34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, natural killer (NK) cell, or other cellular subsets prior to emerging in the graft as a whole.

VII. To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate.

VIII. To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens. When observed, to correlate loss of one HLA haplotype with: a) receipt of a transplant capable of targeting only that haplotype; b) establishment of dominance in a 2 haplotype transplant such that the lost haplotype would be the primary target of the dominant donor; c) being the target of the donor predicted to be more alloreactive in a 2 haplotype transplant.

OUTLINE:

CONDITIONING: Patients undergo total-body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.

After completion of study treatment, patients are followed up for 1 year, and then periodically thereafter.

Arms: arm 1: CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Interventions: intervention 1: Total Body Irradiation (TBI) intervention 2: Donor Lymphocyte Infusion (DLI) intervention 3: Cyclophosphamide (CY) intervention 4: Tacrolimus intervention 5: Mycophenolate Mofetil (MMF) intervention 6: Hematopoietic Stem Cell Transplant (HSCT)
Intervention descriptions: intervention 1: TBI twice daily for 4 days and occurs 6 to 9 days prior to the transplant. Total radiation dose is 12 Gy. intervention 2: DLI given 6 days prior to transplant (HSCT). intervention 3: Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT). intervention 4: Tacrolimus is started the day before the transplant and stops a few months after transplant. intervention 5: MMF is started the day before transplant and stops a few weeks after transplant. intervention 6: CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed using donor cells from two related donors.

The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem cells.

Protocol documents: