Overview

Guadecitabine and Donor Lymphocyte Infusion in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Relapsing After Allogeneic Stem Cell Transplant

Status:
Recruiting
Trial end date:
2021-06-30
Target enrollment:
0
Participant gender:
All
Summary
This phase IIa trial studies how well guadecitabine works in treating patients with acute myelogenous leukemia and myelodysplastic syndrome that has returned after a period of improvement after allogeneic stem cell transplant. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving guadecitabine before the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborators:
Astex Pharmaceuticals
National Cancer Institute (NCI)
Treatments:
Azacitidine
Guadecitabine
Criteria
Inclusion Criteria:

- Diagnosis of AML and MDS according to World Health Organization (WHO) classification
that underwent first allogeneic hematopoietic cell transplant (HSCT) with either
peripheral blood or bone marrow as the source of the hematopoietic stem cells

- No more than 1 antigen mismatch at human leukocyte antigen (HLA)-A, B, C, DRB1 and
DQB1 locus for either related or unrelated donor

- High risk AML and MDS patients will be included; cohort 1: morphological relapse after
stem cell transplant:

- MDS patients: re-appearance of dysplastic changes in the bone marrow, with or
without increase in bone marrow last count, which is pathologically consistent
with myelodysplastic syndrome;

- AML patients: bone marrow blast count >= 5%

- Cohort 2: Persistence or reappearance of minimal residual disease by flow cytometry or
cytogenetic or molecular testing while being in morphological remission after
allogeneic stem cell transplantation

- Cohort 3: High risk AML and MDS patients who are in complete remission morphologically
with no evidence of minimal residual disease by flow cytometry or cytogenetic or
molecular testing after allogeneic stem cell transplantation

- MDS patients:

- Cytogenetics consistent with poor or very poor risk group by 5-risk
classification;

- Cytogenetics consistent with monosomal karyotype

- Bone marrow blast count > 5% but less than 20% at any time during their disease
course before HSCT

- Peripheral blood blast =< 5% at HSCT

- Therapy-related MDS

- AML patients:

- Cytogenetics and molecular features consistent with adverse risk group;

- Presence of minimal residual disease by multi-color flow cytometry or
cytogenetics or molecular studies at the time of HSCT;

- Presence of active disease defined as bone marrow blast count > 5% but less than
=< 10% at the time of HSCT

- Peripheral blood blast count =< 5% at HSCT

- Therapy-related AML

- Be able to start the drug therapy between 42 to 100 days following allogeneic SCT;

- No more than 1 prior allogeneic SCT

- Post-transplant bone marrow consistent with complete remission with no evidence
of minimal residual disease by flow-cytometry or cytogenetics or molecular
testing

- Adequate engraftment within 14 days prior to starting study drug: absolute
neutrophil count (ANC) >= 1.0 x 10^9/L without daily use of myeloid growth
factor; and, platelet >= 50 x 10^9/L without platelet transfusion within 1 week

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

- Serum creatinine =< 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min
as defined by the Cockcroft-Gault equation

- Serum bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate transaminase (aspartate aminotransferase [AST]) or alanine transaminase
(alanine aminotransferase [ALT]) =< 2.5 x ULN

- Alkaline phosphatase =< 2.5 x upper limit (UL)

- No active bleeding

- No uncontrolled graft versus host disease (GVHD)

- No clinical evidence of life-threatening infection

- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent

- Human immunodeficiency virus (HIV) negative and hepatitis B surface antigen (HBs-Ag)
negative

- Negative serum or urine pregnancy test for women with reproductive potential; the only
subjects who will be exempt from this criterion are postmenopausal women (defined as
women who have been amenorrheic for > 12 months) or subjects who have been surgically
sterilized or otherwise proven sterile

Exclusion Criteria:

- Use of any anti-leukemic agents after relapse is documented (note that the use of
these anti-leukemic agents given as post-transplant maintenance therapy is allowed in
this study, e.g., subcutaneous or oral 5-azacytidine or FLT3 inhibitors for
maintenance) for cohorts 1 and 2

- Bone marrow blast count > 60% for cohort 1

- Use of any of the following after transplantation and prior to starting study therapy
for cohort 3:

- Investigational agents/therapies

- Anti-leukemic agents given as post-transplant maintenance therapy (e.g.,
subcutaneous or oral 5-azacytidine or FLT3 inhibitors for maintenance)

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

- Active chronic GVHD that is extensive

- Concurrent use of systemic immune suppressive other than calcineurin inhibitors and
sirolimus

- Active uncontrolled systemic fungal, bacterial or viral infection

- Symptomatic or uncontrolled arrhythmias

- Significant active cardiac disease within the previous 6 months, including: New York
Heart Association (NYHA) class III or IV congestive heart failure; unstable angina or
angina requiring surgical or medical intervention, and/or; myocardial infarction

- Known active viral infection with human immunodeficiency virus (HIV), hepatitis B
virus (HBV) or hepatitis C virus (HCV)

- Prior history of solid tumor unless the subject has been free of the disease for >= 1
year; however, subjects with the following history/concurrent conditions are allowed:
basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix;
carcinoma in situ of the breast; incidental histologic finding of prostate cancer (T1a
or T1b using the tumor, node, metastasis [TNM] clinical staging system)