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)
1. Subject has a hematological malignancy or aplastic anemia (AA) and is undergoing a
first allogeneic transplant procedure.
2. 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)
3. Male or female, age ≥18 years of age
4. Reasonable expectation of survival for at least 3 months, if the transplant procedure
5. Eastern Cooperative Oncology Group (ECOG) status of 0-2 or Karnofsky Performance
Status (KPS) of > 60
6. Transplant Donor
1. 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)
2. 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).
7. Source of the allograft
1. Part 1 (Phase 1: Dose Escalation Phase):Unmodified (non-manipulated) bone
marrow, or mobilized peripheral blood stem cell (PBSC) transplant, using G-CSF
as the mobilizing agent.
2. Part 2: (Phase 2a: Expansion Phase) Unmodified (non-manipulated) bone marrow, or
mobilized peripheral blood stem cell (PBSC) transplant, using G-CSF as the
8. Anti-graft-versus-host disease (GvHD) prophylaxis:
A calcineurin inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination
with either methotrexate (MTX), mycophenolate mofetil (MMF) or sirolimus (RAPA) all
at doses as per the institutional protocols
9. Adequate hepatic function, with bilirubin not exceeding the upper limit of normal
(except when attributed to Gilbert's Disease), and AST and ALT of less than 1.5 times
the upper limit of normal
10. No clinically significant cardiac conduction disorder on screening ECG
11. Serum creatinine ≤ 2.0 mg/dL
12. Female patients of childbearing potential must have a negative serum pregnancy test
prior to enrollment and must agree to use dual method of contraception for 30 days
after study drug administration. Approved methods of contraception include, an IUD
with spermicide, a female condom with spermicide, a diaphragm with spermicide, a
cervical cap with spermicide, use of a condom with spermicide by sexual partner or a
sterile sexual partner.
13. If male, subjects must be sterile or willing to use an approved method of
contraception from the time of Informed Consent to 30 days after study drug
treatment. Males must be willing to refrain from sperm donation within 30 days after
study drug treatment.
14. No clinically significant acute or chronic medical condition that in the opinion of
the investigator will interfere with study participation
15. No clinically significant laboratory abnormalities as determined by the Principal
Investigator, in consultation with the Sponsor's Medical Monitor
16. No active infection
17. Have signed written informed consent before undergoing any study related procedures
and is willing to comply with all study procedures
1. Female subjects who are pregnant or lactating
2. Subjects about to undergo a non-ablative or non-myeloablative transplant
3. AML or ALL patient who are in relapse (>5% blasts) or who are defined as primary
4. Blast crisis CML
5. Radiation, chemotherapy, immunotherapy in the previous 3 weeks, unrelated to the
6. Subjects who, in the judgment of the Investigator have not recovered from the effects
of previous therapy
7. Subject who is about to undergo cord blood transplantation
8. Procedures that are intended to deplete regulatory T-cells from donor transplant
9. Known or suspected HIV infection
10. Active hepatitis A, B, or C infection in recipient or donor
11. Uncontrolled active infection requiring IV antibiotics in recipient or donor
12. Major surgery within 1 month before Day 0
13. Participation in an investigational study within 1 month prior to Day 0
14. Prior treatment with anti-CD3 antibodies
15. Treatment with anti-CD20 antibodies or anti-thymocyte globulin (ATG) within 3 months
of the AHSCT procedure (i.e. infusion of transplant material and RGI-2001).
16. Vaccination within the preceding 2 weeks prior to the planned dose of RGI-2001
17. Planned vaccination within 2 months after study drug administration
18. Known history of cardiac dysfunction (e.g. <50% ejection fraction), ischemia,
conduction abnormalities, or myocardial infarction in the previous six months
19. Cardiac pacemaker or automatic implantable cardioverter-defibrillator
20. Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
QTc interval >450 ms
21. Congenital long QT syndrome or family history of long QT syndrome
22. History of additional risk factors for torsades de pointes (TdP) (e.g., heart
23. Bundle branch block
24. Connective tissue/rheumatologic disorders
25. History of autoimmune disease
26. History of solid tumor, excluding non-melanoma skin or cervical carcinoma after
curative resection, within the preceding 5 years
27. Uncontrolled diabetes
28. Prior allogeneic hematopoietic stem cell transplantation
29. Any other prior organ transplant
30. Psychiatric or addictive disorders that preclude obtaining reliable informed consent
31. Any other condition that, in the opinion of the investigator, renders the subject
unsuitable for study participation