AZD6738 for Patients With Progressive MDS or CMML

NCT03770429 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18-477
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is studying a research drug called AZD6738 as a possible treatment for Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia .

Conditions

Leukemia; Myelodysplastic Syndrome

Keywords

Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Safety of AZD6738 in MDS and CMML (Incidence of dose limiting toxicities)

  Incidence of dose limiting toxicities within the first 28 days of treatment, and enumeration of treatment emergent adverse events graded according to CTCAE

  2 years

Secondary Outcomes (5)

• Overall Response Rate - splicing factor MUT

  2 years

• Overall Response Rate - splicing factor WT

  2 years

• Classification of Toxicity

  2 years

• Overall Survival Rate

  2 years

• Progression Free Survival Rate

  2 years

Other Outcomes (2)

• Factors associated with response/resistance

  2 years

• Biomarkers

  2 years

Study Arms (1)

AZD6738

EXPERIMENTAL

Patients will receive AZD6738 orally on a 28-day cycle

Drug: AZD6738

Interventions

AZD6738 DRUG

MDS and CMML cells rely specifically on the ATR pathway to fix DNA damage and survive; by inhibiting ATR with AZD6738, MDS or CMML cells appear to selectively accumulate DNA damage and die, but healthy cells appear to be less sensitive to this target

AZD6738

Eligibility Criteria

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

You may qualify if:

• Patients must have a diagnosis of recurrent, persistent, or progressive myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) according to WHO 2016 diagnostic criteria:
• For patients with higher-risk MDS (Intermediate, High, or Very High by IPSS-R, score \>3.5), they must have been unresponsive to 4 cycles of decitabine or 6 cycles of azacitidine, progressed on any prior HMA, or intolerant of prior treatment with either azacitidine or decitabine (HMA) chemotherapy.
• For patients with CMML, they must have received prior HMA chemotherapy and have been unresponsive to, progressed on, or be intolerant of this therapy; or those who decline or are not felt to be candidates for HMA chemotherapy.
• Patients with MDS or CMML that has recurred after prior allogeneic stem cell transplantation.
• For patients with lower-risk MDS (Low or Intermediate by IPSS-R, score ≤ 3.5, or any score post-HMA), they must be transfusion-dependent according to IWG criteria and must either be unresponsive to/progressed after prior ESA therapy or have an erythropoietin level \> 500 U/L, who are not felt to be candidates for or lack other treatment options.
• Female and male patients aged ≥ 18 years.
• ECOG performance status ≤2.
• All participants must have adequate organ and marrow function as defined below within 21 days prior to study enrollment:
• Total bilirubin \< 1.5 mg/dL unless due to Gilbert's (\<3.0 mg/dL)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
• INR \< 1.5x ULN
• Creatinine clearance (estimated GFR) ≥45 mL/min/1.73 m2 as measured by the Cockroft-Gault formulation
• Patients enrolled on Part 1 (Dose Finding) of the study need not have splicing factor mutation status known at the time of enrollment but local testing must be initiated or a sample appropriately stored for future testing prior to receiving drug.
• Patients enrolled during Part 2 (Dose Expansion) of the study must have the results of splicing factor mutation testing, per local testing practices, prior to enrollment. Assessment can be performed at any time at or after MDS/CMML diagnosis.
• Part 2 patients enrolled on the splicing factor mutated arm must have at least one of the following mutations:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
• Previous enrollment in the present study.
• Participants with a diagnosis of ataxia telangiectasia.
• Participants who have had systemic chemotherapy within 21 days or five half lives of the medications used, whichever is longer, prior to entering the study.
• Hydroxyurea is allowed if necessary for count control.
• Patients who have received treatment with a small molecule investigational medicinal product (IMP) within 21 days or five half-lives (or 42 days for biologics), whichever is longer, prior to first dose of study drug.
• Participants who have undergone major surgery within 28 days before first dose of study drug.
• Participants who, with the exception of alopecia, have not recovered from any adverse events ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2, unless those toxicities are deemed irreversible and unlikely to interfere with participation on the study per the treating investigator.
• Participants who have had a prior allogeneic transplant must be at least 100 days out from transplant "day 0" and off systemic immunosuppressive therapy without active grade \> 1 GVHD requiring more than 10mg prednisone/day or equivalent.
• Patients receiving systemic corticosteroids may not be on a dose of \> 10mg prednisone/day or equivalent up to 14 days prior to first dose of study drug.
• Participants who are currently receiving any other investigational agents.
• Participants with a diagnosis of/progression to acute myeloid leukemia, per WHO 2016 diagnostic criteria.
• Active CNS involvement of leukemia; evaluation (e.g. lumbar puncture) is not necessary in absence of clinical suspicion.
• Participants with a known hypersensitivity to AZD6738 or any excipient of the product.
• Hematuria +++ on microscopy or dipstick.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• AstraZeneca: collaborator

Study Sites (4)

BIDMC

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

ceralasertib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Andrew M Brunner, MD

  Massachusetts General Hospital

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 1, 2018
• First Posted: December 10, 2018
• Study Start: August 5, 2019
• Primary Completion: April 9, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Requests may be directed to: \[contact information for Sponsor-Investigator or designee\].

Locations

US (4)