RECRUITING

Early Intervention in High Risk CCUS

Conditions

Clonal Cytopenia of Undetermined Significance Cytopenia CCUS

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This research is being done to find out more about the potential risks and benefits of early treatment in participants with high risk Clonal Cytopenia of Unknown Significance (CCUS). This study will give eligible CCUS participants the option of either being observed or taking an oral drug as treatment. The names of the study drug involved in this study is: -Decitabine/cedazuridine (DEC/CED) (a nucleoside metabolic inhibitor and cytidine deaminase inhibitor).

Official Title

A Multi-Site Break Through Cancer Pilot Study Testing the Feasibility and Safety of Therapeutic Intervention for Patients with High-risk Clonal Cytopenia of Undetermined Significance (CCUS)

Quick Facts

Study Start:2025-02-07

Study Completion:2028-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06802146

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥18 years. * Unexplained cytopenia(s) for at least 4 months (at least two separate labs within 4 months including at time of screening must meet this criteria). Cytopenia(s) defined as the presence of ≥ 1 of the following: * Hemoglobin (Hgb) \<12 g/dL for women and \<13g/dL for men * Absolute neutrophil count (ANC) \< 1.8 × 109/L\* * Platelet count (Plt) \<150 × 109/L \Patients known to have a Duffy-null genotype must have anemia (Hgb \< 12g/dL for women, Hgb \<13g/dL for men) and/or thrombocytopenia (Plt \< 150 × 109/L) to be eligible for this study. 1 pathogenic variant detected in any myeloid driver gene with a VAF of at least 0.02 (2%) identified by local next generation sequencing (NGS) of peripheral blood or bone marrow sample within 3 months from screening bone marrow biopsy. * Participants must have a high risk score per the Clonal Hematopoiesis Risk Calculator (CHRS). See APPENDIX C for calculation. * Screening bone marrow biopsy must not be diagnostic of any overt hematologic malignancy by morphologic assessment and must be consistent with a diagnosis of clonal cytopenia of unknown significance (CCUS) as determined by multi-institutional hematopathology review. * ECOG performance status 0-2 (see Appendix A). * Participants must meet the following organ function as defined below: * Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3x upper limit of normal (ULN). * Serum total bilirubin \<1.5x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis or Gilbert's syndrome. In these cases, approval from the study Sponsor-Investigator is required. * Creatinine clearance greater than 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation. * Ability to understand and the willingness to sign a written informed consent document. * For participants of the early pharmacologic intervention cohort: women of childbearing potential must use highly effective contraception during treatment for at least 6 months after the last dose and males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.	* Concurrent primary malignancy requiring active cytotoxic chemotherapy and/or ionizing radiation therapy. * Known inherited bone marrow failure disorder and/or germline predisposition to hematologic malignancy. * Receipt of anti-cancer therapy including any cytotoxic chemotherapy, ionizing radiation therapy, immunomodulatory agents such as lenalidomide, and targeted anti-cancer therapies including PARP inhibitors within the last 6 months. Patients with complete surgical resection of a tumor are not excluded from this study. * Anti-cancer therapy, including any cytotoxic chemotherapy, ionizing radiation therapy, immunomodulatory agents such as lenalidomide and targeted agents such as PARP inhibitors, planned in the next 6 months. Patients on hormonal adjuvant therapy for nonmetastatic breast and prostate cancer or other minimally-myelosuppressive maintenance therapies for non-metastatic cancer may be eligible at the discretion of the study PI. * Diagnosis of MDS, MPN, CMML, AML or any other hematolymphoid malignancy in the patient's lifetime. This includes individuals with MDS-defining chromosomal abnormalities identified via conventional karyotype or FISH. * Presence of a concurrent hematologic malignancy precursor state, such as smoldering multiple myeloma (SMM), and smoldering Waldenstrom's macroglobulinemia. * Presence of an early-stage hematologic precursor state-such as monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B cell lymphocytosis (MBL). * Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment). * Recent (within 3 months) vaccination with any live attenuated vaccine or vaccination with live attenuated vaccine planned during the next 15 months. \Live attenuated vaccines include measles, mumps, rubella (MMR combined vaccine), rotavirus, smallpox, chickenpox, and yellow fever. Laboratory evidence indicative of clinically significant red cell hemolysis. * Hypersplenism and/or evidence of portal hypertension on physical exam or imaging. * Pregnant or lactating.

Inclusion Criteria

Exclusion Criteria

* Age ≥18 years.
* Unexplained cytopenia(s) for at least 4 months (at least two separate labs within 4 months including at time of screening must meet this criteria). Cytopenia(s) defined as the presence of ≥ 1 of the following:
* Hemoglobin (Hgb) \<12 g/dL for women and \<13g/dL for men
* Absolute neutrophil count (ANC) \< 1.8 × 109/L\*
* Platelet count (Plt) \<150 × 109/L \*Patients known to have a Duffy-null genotype must have anemia (Hgb \< 12g/dL for women, Hgb \<13g/dL for men) and/or thrombocytopenia (Plt \< 150 × 109/L) to be eligible for this study.
* 1 pathogenic variant detected in any myeloid driver gene with a VAF of at least 0.02 (2%) identified by local next generation sequencing (NGS) of peripheral blood or bone marrow sample within 3 months from screening bone marrow biopsy.
* Participants must have a high risk score per the Clonal Hematopoiesis Risk Calculator (CHRS). See APPENDIX C for calculation.
* Screening bone marrow biopsy must not be diagnostic of any overt hematologic malignancy by morphologic assessment and must be consistent with a diagnosis of clonal cytopenia of unknown significance (CCUS) as determined by multi-institutional hematopathology review.
* ECOG performance status 0-2 (see Appendix A).
* Participants must meet the following organ function as defined below:
* Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3x upper limit of normal (ULN).
* Serum total bilirubin \<1.5x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis or Gilbert's syndrome. In these cases, approval from the study Sponsor-Investigator is required.
* Creatinine clearance greater than 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation.
* Ability to understand and the willingness to sign a written informed consent document.
* For participants of the early pharmacologic intervention cohort: women of childbearing potential must use highly effective contraception during treatment for at least 6 months after the last dose and males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.

* Concurrent primary malignancy requiring active cytotoxic chemotherapy and/or ionizing radiation therapy.
* Known inherited bone marrow failure disorder and/or germline predisposition to hematologic malignancy.
* Receipt of anti-cancer therapy including any cytotoxic chemotherapy, ionizing radiation therapy, immunomodulatory agents such as lenalidomide, and targeted anti-cancer therapies including PARP inhibitors within the last 6 months. Patients with complete surgical resection of a tumor are not excluded from this study.
* Anti-cancer therapy, including any cytotoxic chemotherapy, ionizing radiation therapy, immunomodulatory agents such as lenalidomide and targeted agents such as PARP inhibitors, planned in the next 6 months. Patients on hormonal adjuvant therapy for nonmetastatic breast and prostate cancer or other minimally-myelosuppressive maintenance therapies for non-metastatic cancer may be eligible at the discretion of the study PI.
* Diagnosis of MDS, MPN, CMML, AML or any other hematolymphoid malignancy in the patient's lifetime. This includes individuals with MDS-defining chromosomal abnormalities identified via conventional karyotype or FISH.
* Presence of a concurrent hematologic malignancy precursor state, such as smoldering multiple myeloma (SMM), and smoldering Waldenstrom's macroglobulinemia.
* Presence of an early-stage hematologic precursor state-such as monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B cell lymphocytosis (MBL).
* Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
* Recent (within 3 months) vaccination with any live attenuated vaccine or vaccination with live attenuated vaccine planned during the next 15 months. \*Live attenuated vaccines include measles, mumps, rubella (MMR combined vaccine), rotavirus, smallpox, chickenpox, and yellow fever.
* Laboratory evidence indicative of clinically significant red cell hemolysis.
* Hypersplenism and/or evidence of portal hypertension on physical exam or imaging.
* Pregnant or lactating.

Contacts and Locations

Study Contact

Maximilian Stahl, MD

CONTACT

(617) 582-7386

maximilian_stahl@dfci.harvard.edu

Principal Investigator

Maximilian Stahl, MD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: Maximilian Stahl, MD

Maximilian Stahl, MD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-07

Study Completion Date2028-12-01

Study Record Updates

Study Start Date2025-02-07

Study Completion Date2028-12-01

Terms related to this study

Keywords Provided by Researchers

Clonal Cytopenia of Undetermined Significance
CCUS
Cytopenia

Additional Relevant MeSH Terms

Clonal Cytopenia of Undetermined Significance
Cytopenia