A Phase 1/2a, Open-Label, Multicenter, Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravenous Administration of RGI-2001 in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT)
Overview
- Phase
- Phase 1
- Intervention
- RGI-2001
- Conditions
- Graft Versus Host Disease
- Sponsor
- Regimmune Corporation
- Enrollment
- 68
- Locations
- 6
- Primary Endpoint
- The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The clinical trial is a Phase 1/2a, open-label, multi-center, dose-escalation study to evaluate the safety, tolerability and pharmacokinetic profile of RGI-2001 in patients undergoing AHSCT, with radiation or non-radiation myeloablative preparative treatment.
The study will be separated into two parts; a dose escalation phase to assess safety, followed by a large expansion phase to further evaluate the pharmacologic effects of either a Maximum Tolerated Dose, Maximum Feasible Dose or optimal pharmacologically active dose of RGI-2001. The initial dose escalation safety portion of the study (Part 1) will include higher risk patients and limit the unrelated donor transplants. After safety is established in part 1 of the study, the second portion of the study will expand the enrollment criteria and allow transplantation by either related or unrelated donors.
This study will endeavor to identify the dose range at which RGI-2001 has an acceptable safety profile, at which biologic activity is observed, and to guide possible dose levels to utilize in later phase studies based on biological activity.
Detailed Description
The clinical trial is a Phase 1/2a, open-label, multi-center, dose-escalation study to evaluate the safety, tolerability and pharmacokinetic profile of RGI-2001 in patients undergoing AHSCT, with radiation or non-radiation myeloablative preparative treatment. In Part 1 (Phase 1: Dose Escalation Phase), patients will receive a single intravenous administration of RGI-2001 approximately 30 minutes after completion of the transplant (either allogeneic PBSCs or allogenic bone marrow transplantation (unmodified)) with the dosage based upon the assigned treatment cohort. Eligible patients will be enrolled in five to seven centers in the United States. Patients who are undergoing AHSCT will be enrolled in a sequential group dose-escalating fashion to determine the safety, tolerability, pharmacokinetic profile, and the MTD or MFD of RGI-2001. It is anticipated that up to six dose levels will be evaluated in Part 1, with an option for an additional cohort (Cohort 7) if the MTD is not reached and pharmacodynamic markers suggest higher doses are warranted. In Part 2 (Expansion Phase), one or more doses below the MTD or MFD will be selected based on a potential correlation between GvHD and biological activity to further assess safety and biologic activity. Approximately 30 patients who are undergoing either allogeneic PBSCs or allogenic bone marrow transplantation (unmodified) will be enrolled in Part 2 of the study. Patients will be monitored for safety for 29 days after the transplant procedure. All patients will be followed for 100 days following transplant procedure for the incidence of acute GvHD, according to the Modified Keystone Criteria for grading acute GvHD (Przepiorka D, et al)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has a hematological malignancy or aplastic anemia (AA) and is undergoing a first allogeneic transplant procedure.
- •Meet one of the following underlying disease criteria:
- •a. Acute myelogenous leukemia (AML) i. First or subsequent morphologic remission b. Acute lymphoblastic leukemia (ALL) i. First or subsequent morphologic remission c. Chronic myelogenous leukemia (CML) i. Chronic phase; or ii. Accelerated phase d. Multiple Myeloma (MM) i. Not more than 20% plasma cells in the bone marrow e. Myelodysplastic syndrome (MDS), including chronic myelomonocytic leukemia (CMML), who have received at least one previous induction regimen and have \<10% blasts f. Myeloproliferative disorder (MPD), including; i. myeloid metaplasia, and ii. myelofibrosis g. Non-Hodgkin's Lymphoma (NHL) i. High-risk NHL in first remission; or ii. Relapsed or refractory NHL h. Hodgkin's lymphoma (HL) beyond first remission i. Aplastic anemia (AA)
- •Male or female, age ≥18 years of age
- •Reasonable expectation of survival for at least 3 months, if the transplant procedure is successful
- •Eastern Cooperative Oncology Group (ECOG) status of 0-2 or Karnofsky Performance Status (KPS) of \> 60
- •Transplant Donor
- •Part 1 (Phase 1: Dose Escalation Phase):
- •Unrelated transplant donor with no more than 1 HLA allele or antigen mismatch, defined as loci A, B, C and DR (note: DQ is excluded)
- •Part 2 (Phase 2a: Expansion Phase):Related or unrelated transplant donor, with no more than 1 HLA allele or antigen mismatch, defined as loci A, B, C and DR (note: DQ is excluded).
Exclusion Criteria
- •Female subjects who are pregnant or lactating
- •Subjects about to undergo a non-ablative or non-myeloablative transplant
- •AML or ALL patient who are in relapse (\>5% blasts) or who are defined as primary refractory
- •Blast crisis CML
- •Radiation, chemotherapy, immunotherapy in the previous 3 weeks, unrelated to the transplant procedure
- •Subjects who, in the judgment of the Investigator have not recovered from the effects of previous therapy
- •Subject who is about to undergo cord blood transplantation
- •Procedures that are intended to deplete regulatory T-cells from donor transplant materials
- •Known or suspected HIV infection
- •Active hepatitis A, B, or C infection in recipient or donor
Arms & Interventions
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: RGI-2001
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: Calcineurin Inhibitors
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: Conditioning Regimen
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: Methotrexate
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: Mofetil Mycophenolate
RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients
Intervention: sirolimus
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: RGI-2001
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: Calcineurin Inhibitors
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: Conditioning Regimen
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: Methotrexate
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: Mofetil Mycophenolate
RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients
Intervention: sirolimus
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: RGI-2001
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: Calcineurin Inhibitors
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: Conditioning Regimen
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: Methotrexate
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: Mofetil Mycophenolate
RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients
Intervention: sirolimus
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: RGI-2001
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: Calcineurin Inhibitors
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: Conditioning Regimen
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: Methotrexate
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: Mofetil Mycophenolate
RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients
Intervention: sirolimus
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: RGI-2001
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: Calcineurin Inhibitors
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: sirolimus
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: Conditioning Regimen
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: Methotrexate
RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients
Intervention: Mofetil Mycophenolate
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: RGI-2001
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: Calcineurin Inhibitors
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: Conditioning Regimen
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: Methotrexate
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: Mofetil Mycophenolate
RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients
Intervention: sirolimus
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: RGI-2001
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: Calcineurin Inhibitors
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: Conditioning Regimen
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: Methotrexate
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: Mofetil Mycophenolate
RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)
Intervention: sirolimus
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: RGI-2001
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: Calcineurin Inhibitors
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: Conditioning Regimen
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: Allogeneic Bone Marrow Transplantation
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: Methotrexate
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: Mofetil Mycophenolate
RGI-2001 + Standard of Care GVHD Prophylaxis
RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
Intervention: sirolimus
Outcomes
Primary Outcomes
The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001
Time Frame: By day 29
The primary outcome measures are: * The incidence and severity of adverse events * The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001, administered as a single intravenous infusion approximately 30 minutes after AHSCT
Secondary Outcomes
- Pharmacodynamic Effects(Within 100 days from AHSCT)
- Pharmacokinetics of RGI-2001(Within first 8 days)
- Efficacy in reducing the intensity of GvHD(Within the first 100 days after AHSCT)
- Optimal Dose of RGI-2001(Within first 100 days after AHSCT)