Haplo Peripheral Blood Sct In GVHD Prevention
Phase 1
Active, not recruiting
- Conditions
- GVHDAMLALLMDSMPNCMMLHodgkin LymphomaNon Hodgkin LymphomaBlood Stem Cell Transplant FailureGraft Vs Host Disease
- Interventions
- Registration Number
- NCT04473911
- Lead Sponsor
- Zachariah Michael DeFilipp
- Brief Summary
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
* 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 25
Inclusion Criteria
-
Men or women ≥ 18 and ≤ 80 years old
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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
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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
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Pulmonary: DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted
-
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen 1: Fludarabine, Cyclophosphamide, and TBI TBI -. 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 Regimen 2: Fludarabine, Melphalan, and TBI TBI -. 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 Regimen 1: Fludarabine, Cyclophosphamide, and TBI RGI-2001 -. 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 Regimen 2: Fludarabine, Melphalan, and TBI RGI-2001 -. 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 Regimen 1: Fludarabine, Cyclophosphamide, and TBI FLUDARABINE -. 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 Regimen 1: Fludarabine, Cyclophosphamide, and TBI CYCLOPHOSPHAMIDE -. 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 Regimen 1: Fludarabine, Cyclophosphamide, and TBI Sirolimus -. 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 Regimen 1: Fludarabine, Cyclophosphamide, and TBI Mycophenolate mofetil -. 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 Regimen 2: Fludarabine, Melphalan, and TBI FLUDARABINE -. 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 Regimen 2: Fludarabine, Melphalan, and TBI Melphalan -. 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 Regimen 2: Fludarabine, Melphalan, and TBI Sirolimus -. 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 Regimen 2: Fludarabine, Melphalan, and TBI Mycophenolate mofetil -. 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 Regimen 2: Fludarabine, Melphalan, and TBI CYCLOPHOSPHAMIDE -. 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
- Primary Outcome Measures
Name Time Method Number of patients achieving successful donor engraftment 60 Days (absolute neutrophil count \> 500/uL and ≥ 90% donor cell chimerism)
- Secondary Outcome Measures
Name Time Method 100-day non-relapse mortality (NRM) rate. 100 Days The regimen will be considered as safe if 100d NRM rate is \<=5%, and not safe if 100d NRM rate is ≥25%.
Trial Locations
- Locations (1)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States