Haplo Peripheral Blood Sct In GVHD Prevention

This research study is studying the RGI-2001 for preventing Graft-vs-Host Disease (GVHD) in people with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), chronic myelomonocytic leukemic (CMML), chemosensitive hodgkin lymphoma (HL), or Non-Hodgkin lymphoma (NHL).who will have a blood stem cell transplantation.

* GVHD is a condition in which cells from the donor's tissue attack the organs.
* RGI-2001 is an investigational treatment

* This is a pilot study in subjects undergoing reduced-intensity haploidentical peripheral blood stem cell transplantation who will receive graft-versus-host disease prevention with post-transplant cyclophosphamide, followed by sirolimus, mycophenolate mofetil, and RGI-2001.
* The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
* The standard of care drugs of fludarabine, cyclophosphamide, melphalan, radiation, sirolimus, and mycophenolate mofetil are all FDA approved.

  * Eligible Participants will be placed in 1 of 2 groups, per physicians discretion:
  * Regimen #1 :

    * Before stem cell transplant:Fludarabine + Cyclophosphamide + Radiation
    * After stem cell transplant: Cyclophosphamide + Sirolimus +Mycophenolate mofetil + RGI-2001
  * Regimen #2

    * Before stem cell transplant: fludarabine + melphalan + radiation
    * After stem cell transplant: cyclophosphamide + sirolimus +Mycophenolate mofetil + RGI-2001
* A total of 20 participants will be enrolled to this trial
* The U.S. Food and Drug Administration (FDA) has not approved RGI-2001 as a treatment for any disease.

Eligibility Criteria:
Inclusion Criteria:

* Men or women ≥ 18 and ≤ 80 years old
* Diagnosis of hematological malignancy:

  * Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in morphologic complete remission
  * Myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), or chronic myelomonocytic leukemic (CMML) with \< 5% blasts in blood or bone marrow
  * Chemosensitive Hodgkin lymphoma (HL) or Non-Hodgkin lymphoma (NHL)
* Patients must be undergoing haploidentical allogeneic hematopoietic cell transplantation, defined as 1st or 2nd degree relative with at least 5/10 matching at HLA-A, -B, -C, DR, and DQ.
* ECOG performance status ≤2
* Patients with adequate physical function as measured by:

  * Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction \>25%
  * Hepatic:

    * Bilirubin ≤ 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis
    * ALT, AST, and Alkaline Phosphatase \< 5 x ULN
  * Renal: Serum creatinine within normal range, or if serum creatinine is outside normal range, then renal function (measured or estimated creatinine clearance or GFR) ≥ 40mL/min/1.73m2
  * Pulmonary: DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Prior allogeneic hematopoietic stem cell transplantation. (Patients may have received a prior autologous hematopoietic stem cell transplant.)
* Participants who are receiving any other investigational agents within 14 days prior to RGI-2001 dosing. Thus, participants must stop investigational agents by Day -9 prior to transplant.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, recent myocardial infarction or stroke, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
* Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.
* Pregnant and breast-feeding women are ineligible because they are not eligible for hematopoietic stem cell transplantation.
* HIV-positive participants and patients with active Hepatitis B or C are ineligible