30 Participants Needed

8-Chloroadenosine + Venetoclax for Acute Myeloid Leukemia

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

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of a new 8-chloroadenosine in combination with venetoclax in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). 8-Chloroadenosine may help block the formation of growths that may become cancer. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving 8-chloroadenosine in combination with venetoclax may help prevent the disease from coming back in patients with acute myeloid leukemia.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot use certain investigational agents, chemotherapy, or specific substances like grapefruit and St. John's Wort close to starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination 8-Chloroadenosine and Venetoclax for treating Acute Myeloid Leukemia?

Research shows that Venetoclax, when combined with low-dose cytarabine, improves survival and response rates in patients with acute myeloid leukemia who cannot undergo intensive chemotherapy. This suggests that Venetoclax can be effective in treating this condition.12345

What safety data exists for 8-Chloroadenosine and Venetoclax in humans?

8-Chloroadenosine has been tested in early clinical trials for blood cancers, and no obvious blood-related toxicity was observed in mice at certain doses. Venetoclax, also known as Venclexta, has been used in various conditions and is generally considered safe, but specific side effects can occur, so it's important to discuss with a healthcare provider.678910

How is the drug combination of 8-Chloroadenosine and Venetoclax unique for treating acute myeloid leukemia?

This treatment is unique because it combines 8-Chloroadenosine with Venetoclax, a drug known for its effectiveness in improving response rates and survival in acute myeloid leukemia (AML) when used with other agents. Venetoclax works by targeting a protein that helps cancer cells survive, and its combination with 8-Chloroadenosine may offer a novel approach to enhance treatment outcomes for AML patients.12111213

Research Team

VP

Vinod Pullarkat

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults (18+) with relapsed or refractory Acute Myeloid Leukemia who have failed at least one line of therapy, are not eligible for stem cell transplant soon, and do not have active central nervous system leukemia or other serious conditions. Participants must be able to swallow capsules, not be pregnant or breastfeeding, and agree to use effective birth control.

Inclusion Criteria

I have relapsed and am not eligible for a specific stem cell transplant.
I am 18 years old or older.
My condition is newly diagnosed acute myeloid leukemia.
See 19 more

Exclusion Criteria

I have no active cancer except possibly skin, bladder, prostate, breast, or cervical cancer that hasn't spread.
I have been diagnosed with acute promyelocytic leukemia.
I cannot swallow pills or have a condition affecting my gut's ability to absorb nutrients.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 8-Cl-Ado intravenously over 4 hours daily on days 1-5 and venetoclax orally once daily on days 1-28. Treatment repeats every 28 days for up to 4 cycles.

16 weeks
Daily visits for 5 days, then weekly visits for 4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 28 days for up to 1 year.

1 year
Follow-up visits every 28 days

Treatment Details

Interventions

  • 8-Chloroadenosine
  • Venetoclax
Trial OverviewThis phase I trial is testing the safety and optimal dosage of a new drug combo: 8-Chloroadenosine with Venetoclax. The goal is to see if this combination can block cancer growth in patients whose AML has returned after treatment or hasn't responded at all.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (8-chloroadenosine, venetoclax)Experimental Treatment2 Interventions
Patients receive 8-Cl-Ado IV over 4 hours daily on days 1-5 and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Find a Clinic Near You

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials
614
Recruited
1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a Phase 3 clinical trial, venetoclax combined with low-dose cytarabine showed improved response rates and overall survival in patients with newly diagnosed acute myeloid leukemia who couldn't undergo intensive chemotherapy, supporting its efficacy.
In an expanded access study in Japan involving 14 patients, the safety profile of venetoclax was consistent with previous findings, with neutropenia being the most common serious side effect, indicating that careful management of adverse events is crucial in clinical practice.
Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan.Asada, N., Ando, J., Takada, S., et al.[2023]
Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.
While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia .Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]
In a study of 211 patients with untreated acute myeloid leukemia (AML) who were not eligible for intensive chemotherapy, venetoclax combined with low-dose cytarabine (LDAC) showed a median overall survival of 8.4 months compared to 4.1 months for the placebo group, indicating a 30% reduction in the risk of death.
The treatment with venetoclax + LDAC also resulted in significantly higher complete response rates (48.3% vs. 13.2%) and improved event-free survival (4.9 months vs. 2.1 months), while maintaining a similar safety profile to the placebo group.
6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150).Wei, AH., Panayiotidis, P., Montesinos, P., et al.[2022]

References

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. [2023]
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). [2022]
Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. [2021]
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]
[Antitumor activities of 8-chloroadenosine in vivo and in vitro]. [2017]
A phase 1 trial of 8-chloro-adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics. [2023]
Preclinical activity of 8-chloroadenosine with mantle cell lymphoma: roles of energy depletion and inhibition of DNA and RNA synthesis. [2021]
ATP directed agent, 8-chloro-adenosine, induces AMP activated protein kinase activity, leading to autophagic cell death in breast cancer cells. [2023]
A novel approach to improve the pharmacokinetic properties of 8-chloro-adenosine by the dual combination of lipophilic derivatisation and liposome formulation. [2018]
11.United Statespubmed.ncbi.nlm.nih.gov
Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. [2023]
Outpatient initiation of venetoclax in patients with acute myeloid leukemia. [2023]
13.United Statespubmed.ncbi.nlm.nih.gov
Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023]