Decitabine + Venetoclax for Blood Cancers

Overseen By Margaret A Thomas, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Decitabine, Venetoclax, ATG

Disqualifiers: HIV, Cirrhosis, Non-hematologic malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of using two drugs, Decitabine (a chemotherapy drug) and Venetoclax (a targeted therapy), alongside a less intense bone marrow transplant for people with certain blood cancers. It specifically targets patients with conditions like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), especially when other treatments are limited or ineffective. Suitable candidates have active AML or high-risk MDS and have a stem cell donor ready. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this combination therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Decitabine, when used with G-CSF (a drug that helps the body produce more blood cells), is generally well-tolerated, though most patients experience some side effects. Common side effects include a decrease in blood cells. In one study, 93% of patients experienced side effects, though not always directly related to the treatment.

When combined with Venetoclax, studies indicate Decitabine remains generally safe, but it can cause more serious side effects for some individuals. About 5% of patients stopped taking Venetoclax due to serious side effects like infections or other health problems. However, another study found that lower doses of these drugs were safe and effective, with few patients needing to reduce their dose or stop treatment due to side effects.

Overall, both treatments are manageable for most patients, but like all medicines, they carry some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Decitabine and Venetoclax for blood cancers because it targets cancer cells in a unique way compared to standard treatments. While traditional therapies often focus solely on killing rapidly dividing cells, Venetoclax works by blocking a protein that helps cancer cells survive, making them more susceptible to being destroyed. This combination with Decitabine, a drug that modifies DNA to stop cancer growth, offers a two-pronged attack on cancer cells. Additionally, the use of G-CSF helps bolster the body's white blood cells, potentially reducing the risk of infection during treatment. This multifaceted approach may lead to more effective and faster responses in patients.

What evidence suggests that this trial's treatments could be effective for blood cancers?

Research has shown that Decitabine, when combined with G-CSF, effectively treats blood cancers. One study found that 82.4% of patients responded to the treatment, and 64.7% achieved complete remission, with no signs of cancer. In this trial, some participants will receive Decitabine with G-CSF. Another promising combination being tested is Decitabine with Venetoclax and G-CSF. A different study reported a 67% overall response rate for this combination in patients with myeloid malignancies, a type of blood cancer. These findings suggest that using Decitabine and Venetoclax together could be a strong option for treating blood cancers. ^{1 3 4 6 7}

Who Is on the Research Team?

Omer A Jamy, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults with certain blood cancers like acute myeloid leukemia or myelodysplastic syndrome, who are suitable for a less intense transplant procedure. Participants should not have other health conditions that could interfere with the study.

Inclusion Criteria

I have a donor for a stem cell transplant who matches the required HLA criteria.

My kidneys are functioning well, with a creatinine clearance over 50 mL/min.

I am mostly able to care for myself.

Exclusion Criteria

I had a stem cell transplant using my own cells less than 3 months ago.

Pregnant and/or breastfeeding

I am allergic to Decitabine, Venetoclax, or ATG.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Administration of G-CSF subcutaneously on days -14 to -10

1 week

In-person visits for G-CSF administration

Treatment

Administration of Decitabine and Venetoclax with dose adjustments based on DLTs

4 weeks

In-person visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Long-term follow-up

Monitoring for regimen-related toxicity and other long-term effects

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Venetoclax

Trial Overview The study tests adding Decitabine and Venetoclax to Fludarabine/Melphalan-based reduced intensity transplants in patients with hematologic malignancies, aiming to improve treatment outcomes.

How Is the Trial Designed?

Group I: Cohort 2: G-CSF + Decitabine + Ven (200mg/d for 7d) Experimental Treatment 3 Interventions

Cohort 2 DL1: G-CSF + Decitabine + Ven (200mg/d for 7d) G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc \>20k. Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10. Venetoclax will be investigated at two dose levels. 200mg daily for 7 days as dose level 1 of cohort 2 of the study and 400mg daily for 7 days as dose level 2. It will be administered orally on from days -12 to -6. Venetoclax 400 and 200 mg/day dose will be adjusted if the patient was on fluconazole (down to 200 and 100 mg/day), posaconazole or isavuconazole (100 and 50 mg/day), and voriconazole (50 and 25 mg/day) If cohort 2 DL1 clears the DLT period based on the criteria discussed previously, then we will start accruing patients to DL2 of cohort 2.

Group II: Cohort 2 DL2: G-CSF + Decitabine + Ven (400mg/d for 7d) Experimental Treatment 3 Interventions

Cohort 2 DL2: G-CSF + Decitabine + Ven (400mg/d for 7d) G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc \>20k. Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10. Venetoclax will be investigated at two dose levels. 200mg daily for 7 days as dose level 1 of cohort 2 of the study and 400mg daily for 7 days as dose level 2. It will be administered orally on from days -12 to -6. Venetoclax 400 and 200 mg/day dose will be adjusted if the patient was on fluconazole (down to 200 and 100 mg/day), posaconazole or isavuconazole (100 and 50 mg/day), and voriconazole (50 and 25 mg/day)

Group III: Cohort 1: G-CSF + Decitabine (100mg/m2 bid for 2d) Experimental Treatment 2 Interventions

Cohort 1 DL1: G-CSF + Decitabine (100mg/m2 bid for 2d) G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc \>20k. Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10.

Group IV: Cohort 1 DL-1: G-CSF + Decitabine (50mg/m2 bid for 2d) Experimental Treatment 2 Interventions

Cohort 1 DL-1: G-CSF + Decitabine (50mg/m2 bid for 2d) G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc \>20k. Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4467448/

Efficacy and safety of decitabine in combination with G-CSF ... Among 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of therapy. The ORR in ...

2. nature.com nature.com/articles/s41598-024-80496-x

Efficacy and safety of the combination of decitabine ... There were 46 patients (74.2%) with complete remission (CR), 5 patients (8.06%) with partial remission (PR), ORR was 82.2%. Main adverse events ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.03277

Effect of rhG-CSF Combined With Decitabine Prophylaxis ... Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118630344

613.Acute Myeloid Leukemia: Clinical Studies The Efficacy ... The Efficacy and Safety of Decitabine in Combination with ATRA, G-CSF and Low Dose Cytarabine(Dlaag Regimen)in Relapsed/Refractory Acute Myeloid Leukemia ...

5. aging-us.com aging-us.com/article/102973

Decitabine in combination with low-dose cytarabine ... After a median follow-up of 12 months (range: 2-82 months), 86 patients (68.8%) had achieved complete remission after one cycle of induction, and 94 patients ( ...

6. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/5108/424715/The-Efficacy-and-Safety-of-Decitabine-in

The Efficacy and Safety of Decitabine in Combination with ... Vitro experiments confirmed that ATRA has an anti-leukemia effect on non-M3-AML cell lines. We perform the 2 phase, single-arm, multicenter ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2895778/

An update on the safety and efficacy of decitabine ... Data collected from this study demonstrated a median survival of 19.4 months by the closure of the study. The most common reported side effect was cytopenias.