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).

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-25

Study Completion Date

2017-05-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Randomised Study of Oral Azacitidine vs Placebo Maintenance in AML or MDS Patients After Allo-SCT

NCT04173533

Acute Myeloid Leukemia Myelodysplasia

ACTIVE_NOT_RECRUITING PHASE3

A Phase II Study of Maintenance With Azacitidine in MDS Patients

NCT00446303

Leukemia, Myelocytic, Acute Myelodysplastic Syndromes

TERMINATED PHASE2

Azacitidine in Treating Patients With Relapsed Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

NCT01083706

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) +9 more

COMPLETED PHASE2

Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

NCT01048034

Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia

COMPLETED PHASE2

5-Azacytidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)

NCT01038635

Leukemia

COMPLETED PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is an open-label, multicenter study of oral azacitidine in MDS or AML patients who have undergone allogeneic HSCT. The study consists of three phases: Screening, Treatment and Follow-up. During the Screening phase, the study doctor will do tests to see if the patient is suitable for this study. The patients meeting protocol-specified entry criteria will enter the treatment phase and be assigned to receive one of the oral azacitidine cohorts. The dosing group of 200 mg QD on Days 1 to 7 will be evaluated first (ie, Cohort 1). In the event that unacceptable toxicity occurs in Cohort 1, then oral azacitidine may be evaluated at lower dose levels (eg, 150 mg). If the dosing regimen is confirmed to be safe in Cohort 1, other cohorts will be evaluated sequentially. During the treatment phase, patients will be monitored closely for safety and tolerability. Dosing interruption or delay, dose or schedule reduction, intra-subject dose/schedule escalation or re-escalation may occur on the basis of protocol-specified dosing adjustment guidelines. Safety will be monitored throughout the study at predetermined intervals and as clinically indicated by vital signs, physical examination, performance status, laboratory tests and evaluation of adverse events. The patient can continue to receive the study treatment for up to 12 months provided that they benefit from the study treatment and all protocol-specified criteria are met. However, the patient may receive the study treatment for less than 12 months due to adverse event, disease recurrence or progression. When the study treatment is discontinued, all patients who have received at least one dose of oral azacitidine will be asked to see the study doctor for the treatment discontinuation visit. Thereafter, all patients discontinued from the study treatment will enter the Follow-up phase for safety and survival follow up.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Leukemia, Myeloid, Acute Myelodysplastic Syndromes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CC-486

Dose of 150 mg, 200 mg, or 300 mg once daily (QD) for the first 7, 10, or 14 days of each 28-day cycle, starting 42-84 days after transplantation.

Group Type EXPERIMENTAL

CC-486

Intervention Type DRUG

Cohorts of 3 to 6 subjects will be treated at escalating or de-escalating sequential dose levels until a preliminary Maximum Tolerated Dose (MTD) is identified.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CC-486

Cohorts of 3 to 6 subjects will be treated at escalating or de-escalating sequential dose levels until a preliminary Maximum Tolerated Dose (MTD) is identified.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Oral Azacitdine

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 \< 20% if MDS or ≤ 10% if AML; and
* Peripheral blood blast ≤ 5%

Be able to start study drug between 42 to 84 days following allogeneic HSCT

Post transplant bone marrow blast count ≤ 5% confirmed within 21 days prior to starting study therapy

Adequate engraftment within 14 days prior to starting study therapy:

* Absolute Neutrophil count (ANC) ≥ 1.0 x 10\^9/L without daily use of myeloid growth factor; and
* Platelet count 75 x 10\^9/L without platelet transfusion within one week.

Adequate organ function:

* Serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x upper limit of normal (ULN)
* Serum bilirubin \< 2 x ULN
* Serum creatinine \< 2 x ULN

Adequate coagulation (Prothrombin time \[PT\] ≤ 15 seconds, Partial thromboplastin time (PTT) ≤ 40 seconds, and/or International normalized ratio \[INR\] ≤ 1.5)

Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL at screening).

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Must agree to follow protocol-specified pregnancy precautions

Exclusion Criteria

* Use of any of the following after transplantation and prior to starting oral azacitidine:

* Chemotherapeutic agents for chemotherapy
* Investigational agents/therapies
* Azacitidine, decitabine or other demethylating agents
* Lenalidomide, thalidomide and pomalidomide

Active Graft-versus-host disease (GVHD) grade II or higher

Any evidence of gastrointestinal (GI) GVHD

Concurrent use of corticosteroids equivalent of prednisone at a dose \> 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No