Haplo Peripheral Blood Sct In GVHD Prevention
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regimen 1: Fludarabine, Cyclophosphamide, and 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 |
Drug: FLUDARABINE
predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles
Other Names:
Drug: CYCLOPHOSPHAMIDE
◦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
Other Names:
Radiation: TBI
Total body irradiation (TBI) once per cycle.
Drug: Sirolimus
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
Other Names:
Drug: Mycophenolate mofetil
◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
Other Names:
Drug: RGI-2001
IV, predetermined dose, weekly to 6 total doses
Drug: CYCLOPHOSPHAMIDE
◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Other Names:
|
| Experimental: Regimen 2: Fludarabine, Melphalan, and 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 |
Drug: FLUDARABINE
predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles
Other Names:
Radiation: TBI
Total body irradiation (TBI) once per cycle.
Drug: Melphalan
Melphalan, infusion, determined dosage, once per cycle
Other Names:
Drug: Sirolimus
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
Other Names:
Drug: Mycophenolate mofetil
◦Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
Other Names:
Drug: RGI-2001
IV, predetermined dose, weekly to 6 total doses
Drug: CYCLOPHOSPHAMIDE
◦Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of patients achieving successful donor engraftment [60 Days]
(absolute neutrophil count > 500/uL and ≥ 90% donor cell chimerism)
Secondary Outcome Measures
- 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%.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02115 |
Sponsors and Collaborators
- Zachariah Michael DeFilipp
- Regimmune Corporation
Investigators
- Principal Investigator: Zachariah DeFilipp, MD, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19-336