Ph2 NK Cell Enriched DCIs w/wo RLR9 Agonist, DUK-CPG-001 From Donors Following Allogeneic SCT

Inclusion Criteria:

1. Patients with hematologic diseases who have undergone T-cell depleted reduced intensity or non-ablative allogeneic transplantation, using a 7-8/8 HLA-matched related or unrelated donor or 4-6/8 HLA-matched related donor. This may include patients with a mixed chimeric state or disease persistence or at high risk of relapse.
2. Performance status must be ECOG PS 0, 1, or 2.
3. Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure.
4. \< Grade 2 acute GVHD at time of the first NK cell-enriched DLI. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned NK cell-enriched DLIs). The dosage/level of immunosuppressive therapy at the time of NK-DLIs should be no greater than 20 mg of prednisone daily or mycophenolate 500 mg bid daily or cyclosporine with a target level of 200 ng/mL or tacrolimus with a target level of 10 ng/mL.
5. Estimated survival of at least 8 weeks.
6. Age of \>= 18 years.
7. Females of childbearing potential should have a negative serum beta-HCG test within 48 hours of beginning DLI and/or DUK-CPG-01 unless contraception is used after initial testing. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
8. Males must agree to use a medically acceptable form of birth control in order to be in this study and for 3 months after infusion

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.
3. Patients likely to have a significantly better durable response to allogeneic transplant alone (better than 60% progression free longer than 2 years) includes: those with myeloproliferative diseases or hemoglobinopathies with over 50% T cell subset engraftment (assessed around 100 days post transplant); It is not anticipated that any such patients would be transplanted within our program, however but those in first remission AML patients with good risk standard genetics or normal genetics with either NPM1 or CEBPA mutations, first chronic phase CML without kinase gene mutations, follicular lymphoma patients in first remission who only required 1 regimen to attain remission all would be excluded from this protocol.

HLA 4-6/8 matched related donor inclusion/exclusion criteria (criterion below are recommended but may evolve to follow current program standards) to be completed within 30 days of apheresis per standard guidelines

1. Adult donors must be an HLA 4-8/8 match with the patient and must be capable of providing informed consent.
2. Potential donors under the age of 18 must have a 'single patient exemption' approved by the IRB. The donor must provide assent and the donor's parent or guardian must provide permission for minor participation. Donors under the age of 18 who cannot assent based on their developmental stage will not be included.
3. Donor must not have any medical condition which would make apheresis more than a minimal risk, and should have the following:

   1. Family members will be considered for donation if they do not have a history of known cardiac problem and do not have abnormal cardiac findings by physical examination. Those with a history of cardiac problems or abnormal cardiac findings by physical examination should undergo a stress evaluation or be evaluated by a cardiologist and deemed eligible to donate.
   2. Documented bilirubin and hepatic transaminases of \< 2.5 x ULN,
   3. Documented adequate hematologic parameters including a hematocrit \> 35% for males and 33% for females, white blood cell count of \>=3,000, and platelets \>=80,000.
   4. FACT labs and final test results available prior to infusion into the patient. In the second donation from the donor, the FACT labs must be redrawn within 30 days of initiation of apheresis. Positive serologies are not repeated as they remain positive for lifetime.
4. Females of childbearing potential should have a negative serum beta-HCG test within 1 week of beginning apheresis. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). A tubal ligation is adequate documentation that a patient is not of child bearing potential.

7-8/8 HLA matched unrelated donors will be matched at least as HLA -A, -B, C and -DRB1. Criterion for donation will be those allowing donation following the NMDP accepted donor criterion and program SOPs for the typical matched unrelated donors.