Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation
Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute, Leukemia, Myelocytic, Chronic
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia, AML, Acute Lymphoblastic Leukemia, ALL, Myelodysplastic Syndrome, MDS
Eligibility Criteria
- ELIGIBILITY CRITERIA:
Inclusion Criteria- Recipient:
Diagnosed with one of the following hematological conditions:
- Acute lymphoblastic leukemia (ALL) of any subtype or
- Acute myelogenous leukemia (AML) of any subtype or
- Myelodysplastic syndrome (MDS) of any subtype or
- Blastic phase Chronic Myeloid Leukemia (CML)
- Relapsed disease within 6 months of matched sibling allogeneic stem cell transplant procedure
- Evaluation for protocol within 8 weeks of relapse and enrollment within 12 weeks or relapse
- 8-75 years of age
- Availability of previous HLA identical (6/6) related donor (ages 8 to 17 must have previously donated bone marrow [not peripheral blood]
- At least one haploidentical (1-3 antigen mismatched) related donor available for apheresis
Exclusion Criteria Recipient (any of the following):
- Active grade II-IV Graft vs. Host Disease (GvHD)
- Extensive chronic Graft vs. Host Disease (GvHD)
- Post-transplant donor lymphocyte infusion (DLI) from original donor within 1 month of protocol enrollment.
- Progressive disease despite post-relapse chemo or monoclonal therapy.
- Co-morbidity of such severity that it would preclude the patients ability to tolerate protocol therapy.
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) greater than 10 x ULN (grade 3, CTCAE).
- Bilirubin greater than 5 x Upper Limit of Normal (ULN) (grade 3, CTCAE).
- Creatinine greater than 3.5 mg/dl (grade 3, CTCAE).
- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation).
- Positive pregnancy test for women of childbearing age.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
Inclusion Criteria- Stem Cell Donors:
- HLA-matched sibling stem cell donor from the original transplant to participate in a stem cell rescue only in the setting of severe, refractory GvHD caused by the haploidentical cells.
- Related HLA haplo-identical (1-3 A, B or DR antigens mismatched with recipient). To maximize the GvL that is associated with HLA disparity, the haploidentical donor will be chosen based on the greatest HLA mismatch (preference: 3/6 greater than 4/6 greater than 5/6). Parents and siblings will be considered equally.
- Weight greater than or equal to 18 kg
- Age greater than or equal to 8 or less than or equal to 80 years old.
Exclusion Criteria Stem Cell Donor (any of the following):
- Pregnant or lactating
- Unfit to receive filgrastim (G-CSF) or previous filgrastim mobilization for donors under 18 years of age.
- Unfit to undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
- Sickling hemoglobinopathies such as HbSS or HbSC.
- HIV positive. Donors who are positive for hepatitis B (HBV), hepatitis C (HCV), human T-cell lymphotropic virus (HTLV-I/II), or T.cruzi (Chagas) will be used at the discretion of the investigator following counseling and approval from the recipient.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation of stem cells unlikely and/or informed consent impossible.
Inclusion criteria- Haplo Lymphocyte Donors:
- Related HLA haplo-identical (1-3 A, B or DR antigens mismatched with recipient). To maximize the GvL that is associated with HLA disparity, the haploidentical donor will be chosen based on the greatest HLA mismatch (preference: 3/6 greater than 4/6 greater than 5/6). Donors age less than 80 years required, and parents and siblings will be considered equally.
- Age greater than or equal to 18 or less than or equal to 80 years old.
Exclusion Criteria Haplo Lymphocyte Donor (any of the following):
- Pregnant or lactating
- Unfit to undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
- Sickling hemoglobinopathies such as HbSS and HbSC .
- HIV positive. Donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II), or T.cruzi (Chagas) will be used at the discretion of the investigator following counseling and approval from the recipient.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation of stem cells unlikely and/or informed consent impossible
Sites / Locations
- National Institutes of Health
Arms of the Study
Arm 1
Experimental
Miltenyi Magnetic cell sorter for CD3
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.