Acute Leukemia, Chronic Leukemia, Myelodysplastic Syndrome, Non-Hodgkins Lymphoma
Conditions
Keywords
ANTITHYMOCYTE GLOBULIN:ATG, FLUDARABINE, THI0TEPA, CliniMACS-CD34 Reagent System, 12-053
Brief summary
Approximately 30% of patients who are candidates for bone marrow transplants do not have an HLA-matched, or close to matched, donor available. For this reason, doctors have been testing ways to make transplants from HLA-partially matched donors as safe and effective as transplants from HLA-matched donors. This study is being done to test the safety and the treatment results of a specific kind of transplant. In this transplant, blood from two donors will be used. Each donor will share one half of your HLA type. Blood from both donors will be transplanted at the same time.
Interventions
BIOLOGICALanti-thymocyte globulin
DRUGthiotepa
DRUGfludarabine phosphate
DRUGmelphalan
RADIATIONtotal-body irradiation (TBI)
PROCEDUREallogeneic hematopoietic stem cell transplantation
BIOLOGICALperipheral blood stem cell transplantation
OTHERlaboratory biomarker analysis
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 19 Years
Healthy volunteers
No
Inclusion criteria
* Malignant conditions for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as: AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t 8;21, t15;17, inv 16). * Secondary AML in 1st remission * AML in 1st relapse or \> 2nd remission * ALL/LL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL \> 2nd remission * 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-Hodgkins lymphoma with chemoresponsive disease in any of the following categories: a) 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): RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for transplantation under protocol IRB 08-008. * Chronic myelomonocytic leukemia: CMML-1 and CMML-2. * Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory aplastic anemia or conjugated cytopenias; non-SCID lethal genetic immunodeficiencies such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, ALPS). * Patients may be of either gender and of any racial or ethnic background. * Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status \> 70%. * Patients must have adequate organ function measured by: Cardiac: asymptomatic or if symptomatic then LVEF at rest must be \> 50% and must improve with exercise. * Hepatic: \< 3x ULN ALT and \< 2.0x ULN 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 CrCl \> 40 ml/min (measured or calculated/estimated) * Pulmonary: asymptomatic or if symptomatic, DLCO \> 50% of predicted (corrected for hemoglobin) * Each patient must be willing to participate as a research subject and must sign an informed consent form.
Exclusion criteria
* Female patients who are pregnant or breast-feeding * Uncontrolled viral, bacterial or fungal infection * Patient seropositive for HIV-I/II; HTLV -I/II * Presence of leukemia in the CNS. Donor Inclusion Criteria: * Each donor must meet criteria outlined by institutional policies * Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter. Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants | 1 year | Efficacy is measured by: 1. incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant. 2. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure 3. incidence and severity of acute and/or chronic GVHD 4. incidence and severity of opportunistic infections developing following engraftment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Recipients Post Transplant | 1 year | The levels of engraftment and persistence of hematopoietic cells and their myeloid and lymphoid progressing from each donor post transplant. The tolerance or 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 parent as measured by standard mixed lymphocyte culture and cell mediated cytolysis assays. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| REGIMEN 1 REGIMEN 1: Patients undergo hyperfractionated TBI TID for a total of 11-12 doses on days -10 to -7 and receive thiotepa IV over 4 hours QD on days -6 and -5, fludarabine phosphate IV over 30 minutes QD on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2.
TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0.
total-body irradiation (TBI)
thiotepa
fludarabine phosphate
anti-thymocyte globulin
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
laboratory biomarker analysis | 0 |
| Regimen 2 To be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days.
TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0.
thiotepa
fludarabine phosphate
melphalan
anti-thymocyte globulin
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
laboratory biomarker analysis | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Regimen 2 | Total | REGIMEN 1 |
|---|---|---|---|
| Age, Continuous | 12 years | 12 years | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants
Efficacy is measured by: 1. incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant. 2. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure 3. incidence and severity of acute and/or chronic GVHD 4. incidence and severity of opportunistic infections developing following engraftment
Time frame: 1 year
Population: Due to the small accrual on study, as well as patient course following treatment on study, the primary objectives of this study were not able to be analyzed.
Secondary
Evaluation of Recipients Post Transplant
The levels of engraftment and persistence of hematopoietic cells and their myeloid and lymphoid progressing from each donor post transplant. The tolerance or 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 parent as measured by standard mixed lymphocyte culture and cell mediated cytolysis assays.
Time frame: 1 year
Population: Due to the small accrual on study, as well as patient course following treatment on study, the primary objectives of this study were not able to be analyzed.