Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT)
Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Hematopoietic Stem Cell Transplant
NCT ID: NCT01379209
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-502
This is a first in man clinical trial that is designed as a two part study in patients undergoing AHSCT. RGI-2001 is believed to have immunomodulating effects that may expand regulatory T-cells and other beneficial cells to modulate the intensity of GvHD after the AHSCT procedure. All patients receive study medication. In Part 1 (Dose Escalation Phase), patients will receive a single intravenous administration of RGI-2001 approximately 30 minutes after completion of the AHSCT, with the dosage based upon the assigned treatment cohort and body weight. Eligible patients will be enrolled in up to four to six centers in the United States. Patients who are undergoing Allogenic Hematopoietic Stem Cell Transplantation (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 seven dose levels will be evaluated in Part 1, with an option for an additional cohort 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 will be enrolled in Part 2 of the study. Patients will be monitored for safety for 29 days after AHSCT. All patients in part 1 and 2 of this study will be followed for 100 days following AHSCT for the incidence of acute GvHD.
Conducting Institutions:
Massachusetts General Hospital, Dana-Farber Cancer Institute
Overall PI:
Yi-Bin Chen, MD,
Massachusetts General Hospital
Site-responsible Investigators:
Contacts:
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
Eligibility Criteria
Inclusion Criteria:
1. Patients with hematological malignancies or myelodysplastic syndrome undergoing
myeloablative therapy and a first allogeneic HSCT (AHSCT)
2. Male or female, age ≥ 18 years of age
3. Eastern Cooperative Oncology Group (ECOG) status of 0-2 or Karnofsky Performance
Status (KPS) of > 60
4. Part 1 Dose Escalation AHSCT Procedure:
1. Patients with hematological malignancies or myelodysplastic syndrome undergoing
a first AHSCT procedure and who are in their 2nd or subsequent remission
2. Type of allograft: Unrelated allogeneic hematopoietic stem cell transplant
donor with no more than 1 HLA allele or antigen mismatch.
3. Source of allograft: Unmodified (non-manipulated) bone marrow.
4. Anti-graft versus host disease (GvHD) prophylaxis will include a calcineuron
inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination with
either methotrexate (MTX) or mycophenolate mofetil (MMF), all at doses as per
the institutional protocols.
5. Part 2 Expansion AHSCT Procedure:
1. Patients with hematological malignancies or myelodysplastic syndrome undergoing
a first AHSCT procedure and who are in their 1st (CR1) or subsequent complete
remission
2. Type of allograft: Related or unrelated allogeneic hematopoietic stem cell
transplant donors with no more than 1 HLA allele or antigen mismatch.
3. Source of allograft: Unmodified (non-manipulated), bone marrow or mobilized
peripheral blood stem cell transplant (PBSCT) using G-CSF as the mobilizing
agent.
4. Anti-graft versus host disease (GvHD) prophylaxis will include a calcineuron
inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination with
either methotrexate (MTX) or mycophenolate mofetil (MMF), all at doses as per
the institutional protocols.
Exclusion Criteria:
1. Female patients who are pregnant or lactating
2. Patients about to undergo mini allogeneic transplant (also known as reduced intensity
transplant, non-ablative or non-myeloablative transplant, or adoptive immunotherapy)
3. Radiation, chemotherapy, immunotherapy in the previous 3 weeks, unrelated to the
AHSCT procedure
4. Patient who is about to undergo cord blood transplantation
5. Procedures that are intended to deplete regulatory T-cells from donor transplant
materials
6. Known or suspected HIV infection
7. Active hepatitis A, B, or C infection in recipient or donor
8. Prior treatment with anti-thymocyte globulin, anti-CD20, or anti-CD3 antibodies
9. Cardiac pacemaker or automatic implantable cardioverter-defibrillator
10. Prior autologous or allogeneic hematopoietic stem cell transplantation
11. Any other prior organ transplant