Phase 2
Completed N=30
Safety Study of Oral Azacitidine (CC-486) as Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS).
Leukemia, Myeloid, Acute · Myelodysplastic Syndromes
Source: ClinicalTrials.gov NCT01835587 ↗
Enrolled (actual)
30
Serious AEs
40.0%
Results posted
Nov 2018
Primary outcomePrimary: The Number of Participants With Dose Limiting Toxicities (DLT) — 0; 0; 0; 1 participants
Summary
The purpose of the study is to determine the maximal tolerated dose and schedule of CC-486, known as oral azacitidine, in patients with AML or MDS after allogeneic hematopoetic stem cell transplant (HSCT). HSCT is more frequently used in AML or MDS as a potential curative therapy. However, disease recurrence/relapse and graft-versus-host disease (GVHD) remain the principal causes of fatal complications after transplantation. Oral azacitidine has significant activity in MDS and AML. Oral azacitidine has also demonstrated immunomodulatory activity in AML patients after allogeneic HSCT. An oral formulation of oral azacitidine provides a convenient route of administration and an opportunity to deliver the drug over a prolonged schedule.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Number of Participants With Dose Limiting Toxicities (DLT) |
0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAE) |
3; 4; 4; 19; 2; 3 | — |
| SECONDARY Percentage of Participants With Graft Versus Host Disease During the Entire Course of the Study |
66.7; 0.0; 75.0; 63.2 | — |
| SECONDARY Kaplan Meier Estimate of Time to Discontinuation From Treatment |
189.0; 177.0; NA; 389.0 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) |
204.6; 253.3; 176.8; 226.7; 187.2 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated to Infinity (AUC-inf; AUC0-∞) Of CC-486 |
206.0; 218.4; 187.5; 232.5; 188.6 | — |
| SECONDARY Maximum Observed Concentration (Cmax) Of CC-486 |
151.9; 149.8; 114.3; 137.85; 91.49 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of CC-486 |
0.77; 2.3; 1.5; 2.0; 2.0 | — |
| SECONDARY Terminal Half-Life (T1/2) of CC-486 |
0.528; 0.575; 0.553; 0.565; 0.446 | — |
| SECONDARY Apparent Total Clearance (CL/F) of CC-486 |
971.1; 1374; 1067; 1290; 795.4 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of CC-486 |
739.9; 1139; 851.3; 1052; 511.8 | — |
| SECONDARY Percentage of Participants With Disease Relapse or Progression |
33.3; 75.0; 0; 15.8 | — |
| SECONDARY Time to Disease Recurrence/Progression |
691.7; 452.5; 660.8; 521.7 | — |
| SECONDARY Overall Survival |
NA; NA; NA; NA | — |
| SECONDARY Kaplan Meier Estimate of Relapse-Free Survival (RFS) |
921.0; 255.0; NA; NA | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed Myelodysplastic Syndromes or Acute Myeloid Leukemia undergoing allogeneic hematopoietic stem cell transplantation with either peripheral blood or bone marrow as the source of hematopoietic stem cells
At the time of allogeneic HSCT:
- No prior allogeneic HSCT; and
- No more than 1 antigen mismatch at Human Leukocyte Antigen (HLA)-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and
- Bone marrow blast 0.5 mg/kg
Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)
Active uncontrolled systemic fungal, bacterial or viral infection
Presence of malignancies, other than MDS or AML, within the previous 12 months
Significant active cardiac disease within the previous 6 months
Data sourced from ClinicalTrials.gov (NCT01835587). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.