Haplo Peripheral Blood Sct In GVHD Prevention

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Reduced Intensity Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Sirolimus/Mycophenolate Mofetil/RGI-2001 Based GVHD Prevention: a Pilot Study

Conditions
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CMML, GVHD, AML, ALL, MDS, MPN, Hodgkin Lymphoma, Non Hodgkin Lymphoma, Blood Stem Cell Transplant Failure, Graft Vs Host Disease, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder, Chronic Myelomonocytic Leukemia, Chemosensitive Hodgkin Lymphoma

Intervention / Treatment
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* Drug: FLUDARABINE
* Drug: CYCLOPHOSPHAMIDE
* Radiation: TBI
* Drug: Melphalan
* Drug: Sirolimus
* Drug: Mycophenolate mofetil
* Drug: RGI-2001
* Drug: CYCLOPHOSPHAMIDE


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen 1: Fludarabine, Cyclophosphamide, and TBI<br>-. Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Two reduced intensity regimens will be allowed, according to the choice of the treating physician Pre- stem cell transplant: Fludarabine predetermined dose, intravenously, 4 times per cycle Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion Total body irradiation (TBI) once during treatment cycle Post stem cell transplant: Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral. Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle RGI-2001: IV, predetermined dose, weekly to 6 total doses | Drug: FLUDARABINE<br>* predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles<br>* Other names: Fludara®;Drug: CYCLOPHOSPHAMIDE<br>* ◦Cyclophosphamide predetermined dose, predetermined number of times in Given in pre-stem cell Regimen #1 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion<br>* Other names: Neosar®;Radiation: TBI<br>* Total body irradiation (TBI) once per cycle.<br>Drug: Sirolimus<br>* Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: Please note that doses of sirolimus can be adjusted at the treating physician's discretion given the multiple drugs and other situations which affect its metabolism<br>* Other names: Rapamune;Drug: Mycophenolate mofetil<br>* ◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle<br>* Other names: Myfortic;Drug: RGI-2001<br>* IV, predetermined dose, weekly to 6 total doses<br>Drug: CYCLOPHOSPHAMIDE<br>* ◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion<br>* Other names: Neosar®;|
| Experimental: Regimen 2: Fludarabine, Melphalan, and TBI<br>-. Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Two reduced intensity regimens will be allowed, according to the choice of the treating physician Pre- stem cell transplant: Fludarabine predetermined dose, intravenously 3 times per cycle Melphalan, infusion, determined dosage, once per cycle Total body irradiation (TBI) once per cycle. Post stem cell transplant Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle RGI-2001: IV, predetermined dose, weekly to 6 total doses | Drug: FLUDARABINE<br>* predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles<br>* Other names: Fludara®;Radiation: TBI<br>* Total body irradiation (TBI) once per cycle.<br>Drug: Melphalan<br>* Melphalan, infusion, determined dosage, once per cycle<br>* Other names: Phenylalanine Mustard;Drug: Sirolimus<br>* Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: Please note that doses of sirolimus can be adjusted at the treating physician's discretion given the multiple drugs and other situations which affect its metabolism<br>* Other names: Rapamune;Drug: Mycophenolate mofetil<br>* ◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle<br>* Other names: Myfortic;Drug: RGI-2001<br>* IV, predetermined dose, weekly to 6 total doses<br>Drug: CYCLOPHOSPHAMIDE<br>* ◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion<br>* Other names: Neosar®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients achieving successful donor engraftment | (absolute neutrophil count > 500/uL and ≥ 90% donor cell chimerism) | 60 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 100-day non-relapse mortality (NRM) rate. | The regimen will be considered as safe if 100d NRM rate is <=5%, and not safe if 100d NRM rate is ≥25%. | 100 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GVHD, AML, ALL, MDS, MPN, CMML, Hodgkin Lymphoma, Non Hodgkin Lymphoma, Blood Stem Cell Transplant Failure, Graft Vs Host Disease, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder, Chronic Myelomonocytic Leukemia, Chemosensitive Hodgkin Lymphoma