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Myelodysplastic SyndromePhase 1NCT05564650

Navitoclax in Relapsed or Refractory High-Risk Myelodysplastic Syndrome

A Phase 1 study testing Navitoclax, Venetoclax and Decitabine in people with Myelodysplastic Syndrome and Recurrent Myelodysplastic Syndrome, run by Thomas Jefferson University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This trial tests the safety, side effects, and best dose of navitoclax in combination with venetoclax and decitabine in treating patients with higher risk myelodysplastic syndrome (MDS) that has come back after initial treatment or was not responsive to initial treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Navitoclax, Venetoclax and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
12 Jan 2023to 8 May 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provide signed and dated informed consent form
  • Willing to comply with all study procedures and be available for the duration of the study
  • Male or female, aged 18 years or older
  • Must have myelodysplastic syndrome with Revised International Prognostic Score (IPSS-R) of at least 3 and have been previously treated with hypomethylating agent (HMA) (azacitidine or decitabine) and venetoclax for at least 2 cycles. Patients in the phase I portion of the trial may be enrolled if they have not received venetoclax with HMA therapy
  • Prior hematopoietic stem cell transplant will be allowed if 90 or more days has passed since the date of transplant to day 1 of cycle 1 and patients are no longer taking immunosuppressive agents
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
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  • Must be able to swallow pills whole
  • Creatinine clearance >= 40 mL/min, calculated with the use of the 24-hour creatinine clearance or modified Cockcroft-Gault equation
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN (or =< 3 x ULN for patients with documented Gilbert syndrome)
  • Coagulation: activated partial thromboplastin time (aPTT) and international normalized ratio (INR) =< 1.5 x ULN
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP)
  • A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. Approved methods are detailed below
  • Hormonal Methods: levonorgestrel-releasing intrauterine system (e.g., Mirena, registered trademark), implants, hormone shot or injection, combined pill, minipill, patch
  • If not surgically sterile, male patients must be willing to practice at least one of the following highly effective methods of birth control for at least their partner's menstrual cycle before and for 120 days after study drug administration.Surgically sterile male patients may practice birth control measures at their own discretion
  • Two of the following barrier/intrauterine methods:
  • Male or female condom with or without spermicide, cap, diaphragm, or sponge with spermicide, copper T intrauterine device
  • Hormonal methods
  • Levonorgestrel-releasing intrauterine system (e.g., Mirena) implants
  • Hormone shot or injection
  • Combined pill
  • Minipill
  • Patch
  • Barrier/intrauterine methods combined with hormonal methods

Who cannot join

  • Active, uncontrolled systemic infection. Patients on prophylactic antibiotics are NOT excluded
  • Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infections defined as detectable viral load
  • History of any active malignancy within the past 2 years prior to screening, with the exception of:
  • Adequately treated carcinoma in situ of the uterine cervix
  • Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
  • Asymptomatic prostate
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  • Subject requiring a medication that interferes with coagulation or platelet function - except for low dose aspirin (up to 100 mg daily) and prophylactic dose low molecular weight heparin (LMWH). Subjects prescribed these medications prior to enrollment should discontinue at least 3 days prior to C1D1. If they are not able to discontinue these medications, subjects will be excluded
  • White blood cells (WBC) > 25,000 cells/microL. Hydroxyurea therapy to reduce WBC count prior to enrollment is NOT excluded
  • Malabsorption syndrome or other condition precluding enteral medication administration
  • Subjects treated concomitantly with CYP2C8 substrates, CYP2C9 substrates, CYP3A inhibitors, CYP3A inducers and P-glycoprotein inhibitors are allowed. Venetoclax dosing must be adjusted. Pregnancy or lactation or intending to become pregnant during the study
  • Pregnancy or lactation or intending to become pregnant during the study
  • Known allergic reactions to components of the study product(s)
  • Treatment with another investigational drug or other intervention within 2 weeks of planned cycle 1 day 1 (C1D1)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase Ib/II Study Evaluating Navitoclax After Failure of Hypomethylating Agent and Venetoclax for Treatment of Relapsed or Refractory High-Risk Myelodysplastic Syndrome

This trial tests the safety, side effects, and best dose of navitoclax in combination with venetoclax and decitabine in treating patients with higher risk myelodysplastic syndrome (MDS) that has come back after initial treatment or was not responsive to initial treatment. This study will also look at the effectiveness of the treatment combination and patient's quality of life while on these medications. Navitoclax is an oral drug that works as an inhibitor of the BCL-2 family of proteins, which are often overly expressed in a wide variety of cancers and are linked to tumor drug resistance. This drug blocks some of the enzymes that keep cancer cells from dying. Venetoclax is an oral drug that works as an inhibitor of BCL-2 proteins that works very similarly to navitoclax by blocking the action of a certain proteins in the body that helps cancer cells survive which helps to kill cancer cells. Decitabine is an intravenous drug. It is a hypomethylating agent which means it interferes with deoxyribonucleic acid (DNA) methylation. DNA methylation is a major factor that regulates gene expression in cells, and an increase in DNA methylation can block the genes that regulate cell division and growth. When these genes are blocked the overall result allows or promotes cancer as there is no control over cell growth. Decitabine stops cells from making DNA and may kill cancer cells. Participation in this trial may improve the understanding of both chemotherapy response in MDS and mechanisms of resistance to current therapies.

Read the detailed description

This trial was intended to be a Phase 1/2 trial but the trial never moved forward to Phase 2.

PRIMARY OBJECTIVES:

  1. To determine the safety profile leading to a recommended phase II dose (RP2D) of navitoclax in combination with venetoclax and decitabine. (Phase I) II. To evaluate the efficacy of combination therapy navitoclax, venetoclax and decitabine in patients with relapsed or refractory high-risk MDS after failure of hypomethylating agent and venetoclax. (Phase II)

SECONDARY OBJECTIVE:

  1. To further evaluate the safety profile navitoclax in combination with venetoclax and decitabine. (Phase II)

EXPLORATORY OBJECTIVES:

  1. To determine relative expression levels of anti-apoptotic BCL-2 family members at baseline and after triplet therapy by intracellular flow cytometry to determine predictive value for response.

II. To compare single cell gene expression at baseline and after triplet therapy.

OUTLINE: This is a phase Ib, dose-escalation study of navitoclax followed by a phase II study.

NAVITOCLAX, VENETOCLAX, \& DECITABINE:

CYCLE 1: Patients receive navitoclax orally (PO) once daily (QD) on days 3-16 in combination with venetoclax PO QD on days 1-16, and decitabine intravenously (IV) on days 3-7. This cycle continues for 30 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy at baseline and day 30, and collection of blood samples at baseline and on days 1 and 15 of cycle.

CYCLE 2 AND BEYOND: Patients receive navitoclax PO QD on days 1-14 of each cycle in combination with venetoclax PO QD on days 1-14 of each cycle, and decitabine IV on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients who achieve a complete response (CR) or marrow complete response (mCR) continue on treatment in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients who have hematologic improvement but who do not attain CR or mCR may continue treatment at the discretion of their treating physician in conjunction with the principal investigator (PI). Patients also undergo bone marrow biopsy on day 28 of cycles 2 and 4 and at end of treatment, as well as collection of blood samples on day 1 of each cycle and at the end of treatment.

After completion of study treatment, patients are followed every 3 months for 12 months. For survival follow-up, patients are followed for 2 years from enrollment of the last patient.

Being tested
Navitoclax, Venetoclax, Decitabine, Bone Marrow Biopsy, Biospecimen Collection
Keywords
Myelodysplastic Syndrome, MDS, high risk MDS, HR-MDS, Relapsed or Refractory, R/R, relapsed or refractory higher-risk myelodysplastic syndrome, acute myeloid leukemia, AML, bone marrow mononuclear cells, BMMC, Navitoclax, Venetoclax, Decitabine, R/R MDS, BCL-2, BCL-XL, MCL-1, BCL-2 family, triplet therapy
Medical subject headings
Myelodysplastic Syndromes, Recurrence, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NavitoclaxBiological

    Also called 923564-51-6, A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

    Given PO

  • VenetoclaxDrug

    Also called 1257044-40-8, 4-(4-((2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide, ABT-0199, ABT-199

    Given PO

  • DecitabineDrug

    Also called 2'-Deoxy-5-azacytidine, 2353-33-5, 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one, 5-Aza-2'-deoxycytidine

    Given IV

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT05564650
Study groupRoleWhat they receive
Treatment (navitoclax, decitabine, venetoclax)ExperimentalThis is a single-center trial of navitoclax, venetoclax and decitabine in adult patients with R/R HR-MDS who have previously failed HMA therapy. This trial was intended to be a Phase 1/2 trial but the trial never moved forward to Phase 2. In the phase I dose escalation portion, patients will receive navitoclax in combination with standard dosing of venetoclax and decitabine. The maximally tolerated dose (MTD) will be the recommended phase II dose (RP2D). Previously, navitoclax in combination with venetoclax and chemotherapy in ALL found the MTD to 50mg of nativoclax po. In the phase II dose expansion portion, patients will receive navitoclax at the RP2D in combination with standard dose venetoclax and decitabine. Patients will continue on treatment with navitoclax, venetoclax and decitabine until relapse, dose-limiting toxicity, availability of alternate therapy or withdrawal of consent.
Receives: Biological: Navitoclax; Drug: Venetoclax; Drug: Decitabine; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximally Tolerated Dose (MTD) of Navitoclax in Combination with Venetoclax and Decitabine (Phase I)

    The Bayesian optimal interval (BOIN) design will be employed to find the MTD. The BOIN design is implemented in a simple way. It is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model based designs.

    Measured: Within 30 days of the first dose of study treatment

  2. Complete Response (CR) Rate (Phase II)

    A 90% confidence interval will be computed for the CR rate by cycle 4.

    Measured: Up to cycle 4, an average of 4 months

Secondary outcomes (11)

  1. Number of Dose-Limiting Toxicities (Phase I)

    Number of dose-limiting toxicities (Phase I)

    Measured: Within 30 days of the first dose of study treatment

  2. Marrow Complete Response Rate (mCR) (Phase II)

    Defined as per International Working Group (IWG) criteria.

    Measured: Up to 2 years from enrollment of the last patient

  3. Hematologic Improvement (HI) rate (Phase II)

    Defined as per IWG criteria.

    Measured: Up to 2 years from enrollment of the last patient

  4. Leukemia Free Survival (LFS) (Phase II)

    LFS defined as the time from the date of randomization to the date of diagnosis of AML or death from any cause, whichever came first.

    Measured: Up to 2 years from enrollment of the last patient

  5. Overall survival (OS) (Phase II)

    Will be estimated using the Kaplan-Meier method, and the median OS along with its corresponding 95% confidence interval will be reported.

    Measured: Up to 2 years from enrollment of the last patient

  6. Change in quality of life (QOL) (Phase II)

    Will be assessed by European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire [EORTC QLQ-C30].

    Measured: At baseline

  7. Change in quality of life (QOL) (Phase II)

    Will be assessed by European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire [EORTC QLQ-C30]

    Measured: At 4 months

  8. Change in quality of life (QOL) (Phase II)

    Will be assessed by European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire [EORTC QLQ-C30]

    Measured: Up to 2 years from enrollment of the last patient

  9. Change in quality of life (QOL) measured by PROMIS-Fatigue (20) (Phase II)

    Change in quality of life (QOL) as assessed by PROMIS-Fatigue (20).

    Measured: At baseline

  10. Change in quality of life (QOL) measured by PROMIS-Fatigue (20) (Phase II)

    Change in quality of life (QOL) as assessed by PROMIS-Fatigue (20)

    Measured: At 4 months

  11. Change in quality of life (QOL) measured by PROMIS-Fatigue (20) (Phase II)

    Change in quality of life (QOL) as assessed by PROMIS-Fatigue (20)

    Measured: Up to 2 years from enrollment of the last patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2022
  2. Study start12 Jan 2023
  3. Primary completion3 May 2024
  4. Study completion8 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05564650
Sponsor's protocol ID
22P.205
Other IDs
JT 17450
Status last verified
May 2026
First submitted
19 Aug 2022
Last updated
19 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Navitoclax, Venetoclax and Decitabine in people with Myelodysplastic Syndrome and Recurrent Myelodysplastic Syndrome, run by Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximally Tolerated Dose (MTD) of Navitoclax in Combination with Venetoclax and Decitabine (Phase I) (time frame: Within 30 days of the first dose of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05564650.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.

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