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

NCT02684162 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2015-0117NCI-2016-00343
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Recurrent Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieved Complete Response (CR)

  Complete remission (CR): Bone marrow with \</= 5% bone marrow blasts with normal maturation of all cell lines in the absence of extramedullary disease in addition to a peripheral blood granulocyte count \>/= 1 X 10\^9/L and a platelet count \>/= 100 x 10\^9 /L.

  Within the first 6 cycles, up to 168 days.

Secondary Outcomes (2)

• Overall Survival (OS)

  At 1 year

• Disease-free Survival

  At 1 year

Study Arms (1)

Treatment (guadecitabine, DLI)

EXPERIMENTAL

Patients receive guadecitabine SC QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive DLI IV over 10-30 minutes on day 6 of cycles 2, 4, and 6 in the absence of disease progression or unacceptable toxicity.

Biological: Donor Lymphocytes; Drug: Guadecitabine; Other: Laboratory Biomarker Analysis

Interventions

Donor Lymphocytes BIOLOGICAL

Given IV

Treatment (guadecitabine, DLI)

Guadecitabine DRUG

Given SC

Also known as: DNMT inhibitor SGI-110, S110, SGI-110

Treatment (guadecitabine, DLI)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (guadecitabine, DLI)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (including chronic myelomonocytic leukemia \[CMML\]) according to 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:

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Betul Oran, MD / Stem Cell Transplantation
• Organization: The University of Texas MD Anderson Cancer Center

BOran@mdanderson.org

713-745-2820

Study Officials

• Betul Oran, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 17, 2016
• Study Start: June 22, 2016
• Primary Completion: October 8, 2024
• Study Completion: October 8, 2024
• Last Updated: November 6, 2025
• Results First Posted: November 6, 2025

Record last verified: 2025-10

Locations

US (1)