Donor Peripheral Blood Stem Cell Transplant in Treating Patients with Hematological Malignancies
This pilot clinical trial studies a donor peripheral blood stem cell transplant in treating patients with hematological malignancies. Giving chemotherapy with or without 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.
Inclusion Criteria
- Malignant conditions for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
- Acute myeloid leukemia (AML) in 1st remission – for patients whose AML does not have ‘good risk’ cytogenetic features (i.e. t8;21, t15;17, inv 16)
- Secondary AML in 1st remission
- AML in 1st relapse or >= 2nd remission
- Acute lymphoblastic leukemia (ALL/LL) in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL >= 2nd remission
- Chronic myelogenous leukemia (CML) failing to respond to or not tolerating imatinib, dasatinib, or nilotinib in first chronic phase of disease; or CML in accelerated phase or second chronic phase
- Non-Hodgkin lymphoma with chemoresponsive disease in any of the following categories: * Intermediate or high grade lymphomas who have failed to achieve a first complete remission (CR) or have relapsed following a 1st remission who are not candidates for autologous transplants * Any non-Hodgkin lymphoma (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 and acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for transplantation under protocol institutional review board (IRB) 08-008
- Chronic myelomonocytic leukemia (CMML): CMML-1 and CMML-2
- Other rare lethal disorders of hematopoiesis and lymphohistiocytosis for which a T-cell depleted transplant is indicated (e.g., hemophagocytic lymphohistiocytosis; refractory; non-severe combined immunodeficiency [SCID] lethal genetic immunodeficiencies such as Wiskott Aldrich syndrome, CD40 ligand deficiency, autoimmune lymphoproliferative syndrome [ALPS])
- Patients must have a Karnofsky (adult) or Lansky (pediatric) performance status >= 70%
- Asymptomatic or if symptomatic then left ventricular ejection function (LVEF) at rest must be >= 50% and must improve with exercise
- < 3 x upper limit of normal (ULN) alanine aminotransferase (ALT)
- < 2.0 x ULN serum bilirubin, unless there is congenital benign hyperbilirubinemia
- Serum creatinine =< 1.2 mg/dl or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 40 ml/min (measured or calculated/estimated)
- Asymptomatic or if symptomatic, diffusing capacity of the lung for carbon monoxide (DLCO) > 50% of predicted (corrected for hemoglobin)
- Each patient much be willing to participate as a research subject and must sign an informed consent form
- DONOR: Each donor must meet criteria outlined by institutional policies
- DONOR: Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter
Exclusion Criteria
- Female patients who are pregnant or breast-feeding
- Uncontrolled viral, bacterial or fungal infection
- Patient seropositive for human immunodeficiency virus (HIV)-I/II; human T-cell lymphotropic virus (HTLV)-I/II
- Presence of leukemia in the central nervous system (CNS)
- DONOR: Evidence of active infection (including urinary tract infection, or upper respiratory tract infection), viral hepatitis exposure (on screening), unless only hepatitis B surface antibody (HBsAb)+ and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) negative, or serologic of exposure or infection with HIV-I/II or HTLV-I/II
- DONOR: If donors do not meet institutional guidelines, exclusion will be considered
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01598025.
PRIMARY OBJECTIVES:
I. To obtain a preliminary estimate of the efficacy of human leukocyte antigen (HLA)-haploidentical biparental T-cell depleted cluster of differentiation (CD)34+ peripheral blood stem cell transplants in the treatment of patients with high risk leukemia, lymphoma, myelodysplastic (MDS) or other lethal disorders of hematopoiesis who lack an HLA compatible related or unrelated donor as measured by: incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant; incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure; incidence and severity of acute and/or chronic graft-versus-host disease (GVHD); and incidence and severity of opportunistic infections developing following engraftment.
SECONDARY OBJECTIVES:
I. To evaluate recipients of biparental HLA haploidentical T-cell depleted CD34+ peripheral blood stem cell transplants at intervals post-transplant as to: levels of engraftment and persistence of hematopoietic cells and their myeloid and lymphoid progressing from each donor post-transplant; the tolerance of reactivity of engrafted T cells from each donor detected in the blood at 3, 6, and thereafter every 3-6 months until normal, post-transplant against host cells and cells derived from the other parents as measured by standard mixed lymphocyte culture and cell mediated cytolysis assays; and the patterns of HLA restriction exhibited by virus antigen-specific T cells detected in the blood at 3, 6, and thereafter every 3-6 months until normal, post-transplant, to determine whether and to what degree these T cells can respond to viral antigens presented by shared HLA alleles in comparison to HLA alleles unique to each parental donor.
OUTLINE: Patients are assigned to 1 of 2 conditioning regimens.
CONDITIONING REGIMEN I: Patients undergo hyperfractionated total body irradiation (TBI) thrice daily (TID) for a total of 11-12 fractions on days -10 to -7 and receive thiotepa intravenously (IV) over 4 hours on days -6 and -5, fludarabine phosphate IV over 30 minutes once daily (QD) on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2.
CONDITIONING REGIMEN II: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2, melphalan IV over 30 minutes on days -8 and -7, thiotepa over 4 hours on days -6 and -5, and anti-thymocyte globulin IV on days -4 to -2.
TRANSPLANTATION: Patients undergo CD34-selected, T cell depleted allogeneic peripheral blood stem cell transplantation (PBSCT) twice, 30 minutes apart, on day 0.
After completion of study treatment, patients are followed up for 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorRichard J. O'Reilly
- Primary ID12-053
- Secondary IDsNCI-2012-00822
- ClinicalTrials.gov IDNCT01598025