Duvelisib + Venetoclax for Chronic Lymphocytic Leukemia

Recruiting at 6 trial locations

Overseen By Celeste Celeste

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Venetoclax, Duvelisib, Coumadin, others

Disqualifiers: HIV, Hepatitis B, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

67 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is assessing a new drug, duvelisib, in combination with a drug that is already FDA approved, venetoclax, as a possible treatment for participants with CLL or those with Richter's Syndrome

Will I have to stop taking my current medications?

The trial requires stopping certain medications that strongly affect the liver enzyme CYP3A at least one week before starting the study drug. If you're on targeted cancer therapies, a washout period (time without taking these medications) of at least five half-lives is needed. Other medications, like corticosteroids under 20 mg daily, are allowed.

Is the combination of Duvelisib and Venetoclax safe for treating Chronic Lymphocytic Leukemia?

Venetoclax, used for treating Chronic Lymphocytic Leukemia (CLL), has been shown to have an acceptable safety profile, with common side effects including diarrhea, neutropenia (low white blood cell count), and nausea. Serious side effects like severe neutropenia and infections are manageable with supportive care and dose adjustments. ^{1 2 3 4 5}

How is the drug combination of Duvelisib and Venetoclax unique for treating Chronic Lymphocytic Leukemia?

The combination of Duvelisib and Venetoclax is unique because it targets two different pathways in cancer cells: Duvelisib inhibits enzymes called PI3K, which are involved in cell growth, while Venetoclax blocks a protein called BCL-2 that helps cancer cells survive. This dual approach may offer a more effective treatment option for Chronic Lymphocytic Leukemia compared to using either drug alone. ^{6 7 8 9 10}

Research Team

Matthew S. Davids

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma needing treatment, or those with Richter's Syndrome after at least one prior therapy (not applicable for Richter's). Must have adequate blood counts, liver and kidney function, agree to use contraception, and be able to consent. Excludes those with central nervous system involvement, recent transplants or active infections, certain virus histories, major surgery within 4 weeks, gastrointestinal disease requiring therapy, pregnancy/breastfeeding individuals.

Inclusion Criteria

My liver is working well.

Ability to understand and the willingness to sign a written informed consent document

I have been diagnosed with CLL/SLL needing treatment or have DLBCL due to Richter's Syndrome.

Exclusion Criteria

I am taking less than 20 mg of corticosteroids daily.

I have a lung condition or severe breathing problems.

Known hypersensitivity to duvelisib and/or its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the safe dose of venetoclax with duvelisib and observe side effects

7 weeks

Participants admitted for initial dose of venetoclax at each dose escalation

Phase II Treatment

Evaluate the effectiveness of duvelisib and venetoclax combination for CLL or Richter's Syndrome

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Duvelisib
• Venetoclax

Trial Overview The trial is testing a new drug called duvelisib in combination with an FDA-approved drug venetoclax. It aims to treat participants who have relapsed or are not responding well to previous treatments for CLL/SLL/RS. The study will assess the effectiveness and safety of this drug combo.

Participant Groups

Group I: Duvelisib +Venetoclax, Experimental Treatment 2 Interventions

Duvelisib will be given alone for the first seven days. On day 8 Venetoclax will be added. * Duvelisib will be administered orally twice daily * Venetoclax will be administered orally daily * All patients will be admitted for administration of the initial dose of venetoclax at each dose escalation

Duvelisib is already approved in United States for the following indications:

Approved in United States as Copiktra for:

• Relapsed or refractory chronic lymphocytic leukemia (CLL)
• Relapsed or refractory small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Secura Bio, Inc.

Industry Sponsor

Trials

9

Recruited

200+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

Venetoclax, an oral BCL-2 inhibitor, is an effective long-term treatment for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), particularly those with high-risk features like chromosome 17p deletion, based on a safety analysis of 350 patients.

The treatment is generally well tolerated, with manageable side effects; however, common adverse events included diarrhea (41%), neutropenia (40%), and nausea (39%), and serious infections occurred in 15% of patients, indicating the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Davids, MS., Hallek, M., Wierda, W., et al.[2019]

The study established the maximum tolerated dose (MTD) for the combination treatment NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma, with 32 out of 56 patients receiving the MTD, indicating a manageable safety profile despite some patients experiencing severe treatment-related adverse events.

Patients treated with NALIRIFOX showed a median progression-free survival of 9.2 months and overall survival of 12.6 months, suggesting that this treatment regimen may be effective for this difficult-to-treat cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. Wainberg, ZA., Bekaii-Saab, T., Boland, PM., et al.[2021]

In a phase III study involving 220 previously untreated patients with metastatic colorectal cancer, both treatment sequences (FOLFIRI followed by FOLFOX6 and vice versa) resulted in similar median survival rates of approximately 21.5 months and 20.6 months, indicating comparable efficacy.

The study revealed distinct toxicity profiles for each treatment sequence, with FOLFIRI causing more mucositis and nausea/vomiting, while FOLFOX6 was associated with higher rates of neutropenia and neurosensory toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. Tournigand, C., André, T., Achille, E., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Effects of bevacizumab on plasma concentration of irinotecan and its metabolites in advanced colorectal cancer patients receiving FOLFIRI with bevacizumab as second-line chemotherapy. [2018]

7. Australia pubmed.ncbi.nlm.nih.gov

Effects of bolus injection of 5-fluorouracil on steady-state plasma concentrations of 5-fluorouracil in Japanese patients with advanced colorectal cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical outcome of elderly patients with metastatic colorectal cancer treated with FOLFOXIRI versus FOLFIRI: Subgroup analysis of a randomized phase III trial from the Hellenic Oncology Research Group (HORG). [2013]

10. United States pubmed.ncbi.nlm.nih.gov

FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. [2023]