Acute Myelogenous Leukemia (AML) - Relapsed, Primary Refractory Disease or Poor Risk Factors, Chronic Myelogenous Leukemia (CML) - Accelerated or Second Chronic Phase, Myelodysplastic Syndrome (MDS) - High and Intermediate Risk, Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL) - Refractory
Conditions
Brief summary
To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant. To assess the incidence of acute GvHD during the first 100 days after transplantation.
Detailed description
To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant; assess the incidence of acute GvHD during the first 100 days after transplantation; and assess platelet engraftment, graft failure, chronic GvHD, clinical safety, and devise performance.
Interventions
DEVICECliniMACS System
The CliniMACS System is a cell selection device consisting of the following components: 1. Computer-controlled instrument; 2. Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix) 3. Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle) 4. Wash buffer
Sponsors
Ginna Laport
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
RECIPIENT INCLUSION CRITERIA Histopathologically-confirmed diagnosis of hematological or lymphatic malignancy, defined as one of the following: * Acute myeloid leukemia (AML) as primary refractory disease, or in relapse * Acute leukemia in first remission with poor risk factors and molecular prognosis * AML with -5,-7, t(6;9), tri8, -11 * Acute lymphocytic / lymphoblastic leukemia (ALL) with Phil+ t(9;22),(q34;q11.2), and t(4:11)(q21;23) * Chronic myelogenous leukemia (CML in accelerated, second chronic phase * Myelodysplastic syndrome with high intermediate to high risk categories * Non-Hodgkin's lymphoma (NHL) * Chronic lymphocytic leukemia (CLL), Refractory \< 50 years old at time of registration Donor is related Donor is genotypically-matched and haploidentical for HLA-A, B,C and DRB1, DQ loci Donor differs for 2 or 3 HLA alleles on the unshared haplotype in the GvHD direction No HLA-matched sibling or matched unrelated donor is identified ECOG performance status not more than 2 LVEF \> 45% DLCO \> 50% corrected for hemoglobin Serum creatinine * \< 1.5 mg/dL OR * creatinine clearance \> 50 mL/min for those above serum creatinine of 1.5 mg/dL serum bilirubin \< 2.0 mg/dL ALT \< 2x ULN (unless secondary to disease) Females of childbearing potential must have a negative serum or urine beta-HCG test within 3 weeks of registration No prior cancer within 5 years with the exception of surgically-cured, non-melanoma skin cancer or in situ cancer of the cervix No prior myeloablative therapy or transplant Duly-executed informed consent RECIPIENT
Exclusion criteria
Suitable candidate for autologous transplantation Participation in other investigational drugs or devices trials that might influence the study endpoints Evidence of active hepatitis Evidence of active cirrhosis HIV-positive History of invasive aspergillosis Presence of any other uncontrolled, active infection, ie, bacterial, viral or fungal Uncontrolled CNS involvement Documented allergy to murine proteins Documented allergy to iron dextran Lactating female Female of child-bearing potential unwilling to implement adequate birth control Medical problem / neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and/or to tolerate transplantation, in the opinion of the principal investigator Medical problem / neurologic/psychiatric dysfunction which would prolong hematologic recovery and place the recipient at unacceptable risk, in the opinion of the principal investigator would . DONOR INCLUSION CRITERIA Age \< 60 years Weight \> 25 kg Medical history and physical examination confirm good health status as defined by institutional standards Within 30 days of apheresis collection, seronegative for HIV assessed as HIV Ag; HIV 1+2 Ab; or HTLV I/II Ab Within 30 days of apheresis collection, seronegative for hepatitis assessed as HBsAg; HBcAb (IgM and IgG); or HCV Ab Within 30 days of apheresis collection, seronegative for syphilis assessed as RPR Genotypically haploidentical as determined by HLA typing Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within 3 weeks of mobilization Capable of undergoing leukapheresis Has adequate venous access Willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate Agreeable to second donation of PBPC (or a bone marrow harvest) should the recipient fail to demonstrate sustained engraftment following the transplant Duly-executed informed consent Screened for CMV seroreactivity * Must be seronegative donor if recipeint is seronegative. * Otherwise the donor will be selected on the ability of NK cell alloreactivity based upon HLA typing results and donors who are capable of NK cell alloreactivity will be used preferentially. DONOR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil Engraftment | 30 days post-transplant | Number of subjects recovering neutrophils, assessed as 1st of 3 consecutive days on which ANC \> 0.5x10e9/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute GvHD (Grade II-IV) | within 100 days post-transplant | Number of subjects with acute GvHD (grade II-IV) within 100 days post-transplant, per the Consensus Conference on Acute GvHD Grading (Przepiorka D, et al. Bone Marrow Transplantation. 1995. 15:825-828). |
| Platelet Recovery | 40 days | Number of subjects recovering platelets to \> 20x10e9/L, assessed on the 7th day unsupported by platelet transfusions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Haploidentical Allogeneic Transplant Using CliniMACS System The CliniMACS cell selection system (Miltenyi Biotec) will be used to enrich hematopoietic stem cells from related, haploidentical, HLA-matched donors, who matched on the A,B,C and DRB1, DQ loci.
The CliniMACS System is a cell selection device consisting of the following components:
1. Computer-controlled instrument;
2. Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix)
3. Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle)
4. Wash buffer | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Haploidentical Allogeneic Transplant Using CliniMACS System |
|---|---|
| Age, Continuous | 27 years |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 3 / 13 |
Outcome results
Primary
Neutrophil Engraftment
Number of subjects recovering neutrophils, assessed as 1st of 3 consecutive days on which ANC \> 0.5x10e9/L
Time frame: 30 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haploidentical Allogeneic Transplant Using CliniMACS System | Neutrophil Engraftment | 12 participants |
Secondary
Acute GvHD (Grade II-IV)
Number of subjects with acute GvHD (grade II-IV) within 100 days post-transplant, per the Consensus Conference on Acute GvHD Grading (Przepiorka D, et al. Bone Marrow Transplantation. 1995. 15:825-828).
Time frame: within 100 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haploidentical Allogeneic Transplant Using CliniMACS System | Acute GvHD (Grade II-IV) | 1 participants |
Secondary
Platelet Recovery
Number of subjects recovering platelets to \> 20x10e9/L, assessed on the 7th day unsupported by platelet transfusions
Time frame: 40 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haploidentical Allogeneic Transplant Using CliniMACS System | Platelet Recovery | 12 participants |