Guadecitabine and Atezolizumab in Treating Patients With Advanced Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia That Is Refractory or Relapsed

NCT02935361 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 9L-16-3NCI-2016-01233P30CA014089
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

This phase I/II trial studies the side effects and best dose of guadecitabine when given together with atezolizumab and to see how well they work in treating patients with myelodysplastic syndrome or chronic myelomonocytic leukemia that has spread to other places in the body and has come back or does not respond to treatment. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of cancer cells to grow and spread. Giving guadecitabine and atezolizumab may work better in treating patients with myelodysplastic syndrome or chronic myelomonocytic leukemia.

Conditions

Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

  Descriptive summaries and analyses of CTCAE 4.0 toxicities that occur will be produced, both by patient and by cycle.

  Up to 56 days

• Overall response (complete response [CR] + partial response + marrow CR + hematological improvement) (Phase II)

  Up to 168 days

Secondary Outcomes (6)

• Incidence of grade 3 or higher adverse events and grade 2 toxicities that do not resolve after 3 weeks assessed by CTCAE 4.0

  Up to 8 weeks

• Overall response rate (Phase II)

  Up to 4 years

• Overall survival

  From start of treatment to death from any cause, assessed up to 4 years

• Percentage of patients who were transfusion-dependent on study entry who become transfusion-independent

  Up to 4 years

• Progression free survival

  From start of treatment to the first disease progression or recurrence, assessed up to 4 years

Other Outcomes (6)

• Degree of PD-L1 expression assessed in bone marrow, T cells, and malignant cells by immunohistochemistry or flow cytometry

  Up to 4 years

• PD-1 expression by T cells and malignant cells

  Up to 4 years

• Percentage of T cells expressing PD-1/methylation levels

  Up to 4 years

Study Arms (1)

Treatment (guadecitabine, atezolizumab)

EXPERIMENTAL

Patients receive guadecitabine SC on days 1-5 and atezolizumab IV over 30-60 minutes on days 8 and 22. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Guadecitabine

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (guadecitabine, atezolizumab)

Guadecitabine DRUG

Given SC

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

Treatment (guadecitabine, atezolizumab)

Eligibility Criteria

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

You may qualify if:

• Phase I: Adult subjects with advanced MDS requiring therapy who were previously treated with either azacitidine or decitabine for at least 4 cycles and deemed to have failed therapy due to progression of disease using International Working Group (IWG) criteria ("refractory") or losing their previously documented response to the therapy ("relapsed")
• Phase II: Adult subjects with advanced MDS requiring therapy who were previously treated with either azacitidine or decitabine for at least 4 cycles and deemed to have failed therapy due to progression of disease using IWG criteria ("refractory") or losing their previously documented response to the therapy ("relapsed")
• MDS should be classified as:
• Intermediate 1-risk or higher risk according to the international prognostic scoring system (IPSS) or revised IPSS
• Chronic myelomonocytic leukemia (CMML)
• Cytomorphology to confirm bone marrow blasts;
• Cytogenetics; AND
• Eastern Cooperative Oncology Group (ECOG) status 0-2
• Subject is able to understand and willing to comply with protocol requirements and instructions
• Subject has signed and dated informed consent
• Total bilirubin (except for Gilbert's syndrome) =\< 2.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (ALT) and alanine aminotransferase (AST) =\< 3 x ULN
• Creatinine =\< 2.5 x ULN
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 90 days after the last dose of atezolizumab
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)

You may not qualify if:

• Any active history of a known autoimmune disease; subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with a history of interstitial lung disease; patients requiring continuous supplemental oxygen are excluded to avoid possible complications from pneumonitis
• History of idiopathic pulmonary fibrosis, organizing pneumonitis (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis
• Patients who are actively receiving any other anticancer therapy
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to HMAs
• Patients with a diagnosis of acute myeloid leukemia (AML) not transformed from MDS or transformed from MDS with \> 30% blasts in bone marrow or white blood cells (WBC) \> 25 x 10\^3/L
• Patients with short life expectancy (less than 3 months) due to comorbidity other than MDS
• Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotropin \[B-hCG\] pregnancy test)
• Patients with current alcohol or drug abuse
• Patients who have received treatment with an investigational drug within 30 days preceding the first dose of study medication
• Patients with uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with prior infections must be afebrile for \>= 72 hours and completed any antibiotics prior to receiving study drug
• In patients who received IV antibiotics for active infection, a washout period of 14 days is required prior to initiating study therapy (exception: patients with febrile neutropenia in whom no infectious etiology has been determined/documented)
• Patients receiving chronic antimicrobial prophylaxis therapy (e.g. antifungal prophylaxis) may be included in the study provided there is no active infection
• Patients infected with hepatitis B, C or human immunodeficiency virus (HIV), unless they are on stable and effective antiviral treatment

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Van Andel Research Institute: collaborator

Study Sites (4)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

atezolizumab; guadecitabine

Condition Hierarchy (Ancestors)

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

Study Officials

• Casey O'Connell

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2016
• First Posted: October 17, 2016
• Study Start: November 2, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)