Venetoclax for Blastic Plasmacytoid Dendritic Cell Neoplasm

Not currently recruiting at 1 trial location

Overseen By Jeremy M Stewart

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Venetoclax, CYP3A inducers, CYP3A inhibitors

Disqualifiers: HIV, Hepatitis B/C, Cardiopulmonary disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called venetoclax to determine its effectiveness in treating blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare blood cancer. The study aims to identify a safe and effective dose. Ideal participants are those diagnosed with BPDCN whose condition has worsened despite previous treatment. Individuals newly diagnosed with BPDCN may also qualify if they cannot tolerate strong chemotherapy due to other health issues. Participants must take the drug daily and attend regular study visits. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have taken chemotherapy, radiation, or biologic cancer therapy within 14 days before starting the trial. Also, you should avoid certain foods and medications that affect liver enzymes within a week before starting the study.

Is there any evidence suggesting that Venetoclax is likely to be safe for humans?

Research shows that venetoclax is usually well-tolerated by patients. Studies have found that cells from BPDCN, a rare blood cancer, are very sensitive to venetoclax. This drug targets a protein called BCL-2, which helps cancer cells survive. Venetoclax blocks this protein, hindering cancer cell growth.

The FDA has already approved venetoclax for treating some types of leukemia, providing existing safety information from its use in other conditions. However, since this trial is in its early stages, the main goal is to find a safe dose for BPDCN patients. While venetoclax shows promise, monitoring for any side effects during the trial remains crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Venetoclax is unique because it targets a specific protein called BCL-2, which helps cancer cells survive. While traditional treatments for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) often involve chemotherapy or stem cell transplants, Venetoclax offers a more targeted approach by directly inducing cancer cell death. Researchers are excited about Venetoclax because its daily oral administration provides a potentially less invasive and more convenient alternative to existing treatments, which may improve patient quality of life.

What evidence suggests that Venetoclax might be an effective treatment for BPDCN?

Research suggests that venetoclax, the treatment under study in this trial, could be a promising option for a rare cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). Studies have found that BPDCN cells rely on a protein called BCL-2 for survival. Venetoclax blocks this protein, making it easier for the cancer cells to die. In lab tests, BPDCN cells responded well to venetoclax, indicating its potential effectiveness against the disease. One case report described a patient who became disease-free after using venetoclax, although the cancer returned after six weeks. While more research is needed, these findings support venetoclax's potential in treating BPDCN. ^{3 6 7 8 9}

Who Is on the Research Team?

Andrew Lane, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with BPDCN that's come back or didn't respond to treatment, except hydroxyurea. They must have decent organ function and be able to consent. Women who can have babies and men must use birth control during the study. It's also open to those over 75 or unfit for intensive chemo.

Inclusion Criteria

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

My BPDCN has not improved or has returned after at least one treatment (not counting hydroxyurea).

I have BPDCN, have tried at least one treatment (not hydroxyurea), or am over 75 years old and haven't started treatment, or am over 18 and can't or won't do intensive chemotherapy.

Exclusion Criteria

Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or Star fruit within 3 days prior to the initiation of study treatment

I have been treated with venetoclax before.

I haven't had cancer treatment in the last 14 days, except for hydroxyurea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Venetoclax daily to determine the safest dose using a modified 3+3 dose-escalation design

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax

Trial Overview The trial is testing Venetoclax as a potential treatment for BPDCN. Participants will receive this drug to see how effective it is against their condition.

How Is the Trial Designed?

Group I: Venetoclax Experimental Treatment 1 Intervention

* Venetoclax is administered on a daily basis orally. * The investigators will use a modified 3+3 with a de-escalation dose level design to establish the appropriate and tolerable dose of venetoclax.

Venetoclax is already approved in United States, European Union for the following indications:

Approved in United States as Venclexta for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Approved in European Union as Venclyxto for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

DX-8951f (exatecan mesylate) was administered to 36 patients with advanced solid tumors, showing a maximum-tolerated dose of 0.5 mg/m²/day for minimally pretreated patients and 0.3 mg/m²/day for heavily pretreated patients, with manageable toxicity primarily involving brief neutropenia.

The treatment demonstrated preliminary anticancer activity, with partial responses in patients with various resistant cancers, suggesting that DX-8951f could be a promising option for further evaluation in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies. Rowinsky, EK., Johnson, TR., Geyer, CE., et al.[2017]

The maximum-tolerated dose (MTD) of Exatecan mesylate (DX-8951f) for patients with advanced solid tumors was determined to be 2.4 mg/m², with granulocytopenia identified as the dose-limiting toxicity (DLT) for minimally pretreated patients.

While no complete or partial responses were observed, four patients achieved stable disease, indicating some level of efficacy; the pharmacokinetic profile of DX-8951f was linear, suggesting predictable behavior at the administered doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. Royce, ME., Hoff, PM., Dumas, P., et al.[2017]

Exatecan can be safely administered as a continuous intravenous infusion (CIVI) for 21 days at a maximum tolerated dose of 0.15 mg/m²/day, with manageable side effects primarily related to blood cell counts.

The study showed preliminary evidence of anticancer activity, with partial responses observed in two heavily pretreated patients, suggesting that exatecan may be effective against certain drug-resistant cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I and pharmocokinetic study of exatecan mesylate administered as a protracted 21-day infusion in patients with advanced solid malignancies. Garrison, MA., Hammond, LA., Geyer, CE., et al.[2017]

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]

In a study involving 272 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), higher concentrations of venetoclax led to a quicker reduction in lymphocyte counts and tumor size, resulting in a high objective response rate (ORR) of 84.8% at a daily dose of 400 mg.

Importantly, increasing the dose of venetoclax did not correlate with a higher risk of serious adverse events like neutropenia or infections, suggesting that the 400 mg daily regimen is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. Freise, KJ., Jones, AK., Eckert, D., et al.[2018]

In a study of 43 patients with light-chain amyloidosis (AL) treated with venetoclax, the overall hematologic response rate was 68%, with 63% achieving very good partial response (VGPR) or complete response (CR), indicating that venetoclax is an effective treatment option for AL.

Patients with the t(11;14) genetic alteration had significantly better outcomes, with an 81% hematologic response rate and a median progression-free survival (PFS) that was not reached, compared to 40% response and a median PFS of 6.7 months for those without this alteration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis. Premkumar, VJ., Lentzsch, S., Pan, S., et al.[2021]

In a phase I study involving 48 patients with relapsed or refractory multiple myeloma (RRMM), the combination of venetoclax with daratumumab and dexamethasone (VenDd) showed a remarkable overall response rate of 96%, indicating its strong efficacy, especially in patients with the t(11;14) translocation.

The combination of venetoclax with bortezomib, daratumumab, and dexamethasone (VenDVd) also demonstrated significant efficacy, with a 92% overall response rate, and an 18-month progression-free survival rate of 66.7%, suggesting that these combinations could provide durable responses in RRMM treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). Bahlis, NJ., Baz, R., Harrison, SJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12366441/

Venetoclax in the Therapeutic Strategy for BPDCN Management Venetoclax, a B‐cell lymphoma 2 (BCL‐2) inhibitor, is a promising treatment for blastic plasmacytoid dendritic cell neoplasm (BPDCN) and is ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6499443/

Evaluating venetoclax and its potential in treatment-naïve ... Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute ...

3. aacrjournals.org aacrjournals.org/cancerdiscovery/article/7/2/156/5885/Blastic-Plasmacytoid-Dendritic-Cell-Neoplasm-Is

Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent ... We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and were uniformly sensitive to the BCL2 inhibitor venetoclax, as measured by ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04216524

Study Details | NCT04216524 | Venetoclax, SL-401, and ... This phase II trial studies how well venetoclax, SL-401, and chemotherapy works in treating patients with blastic plasmacytoid dendritic cell neoplasm.

5. researchgate.net researchgate.net/publication/372903899_Blastic_plasmacytoid_dendritic_cell_neoplasm_challenges_in_diagnosis_and_treatment_with_potential_of_venetoclax_as_an_alternative_to_vincristine_in_high-risk_patients-a_case_report

Blastic plasmacytoid dendritic cell neoplasm The patient achieved a disease-free state for the first time in disease course, maintaining it for a period of over six weeks before experiencing a relapse.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5296248/

Blastic plasmacytoid dendritic cell neoplasm is dependent on ... We found that primary BPDCN cells were dependent on the anti-apoptotic protein BCL-2 and were uniformly sensitive to the BCL-2 inhibitor venetoclax.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07007052?cond=Dendritic%20cell%20tumor%20OR%20%22%22&aggFilters=status:not%20rec&viewType=Table&rank=3

NCT07007052 | Phase II Study Evaluating the Efficacy and ... The goal of this clinical trial is to study the efficacy of the tagraxofusp + venetoclax combination in treatment-naive blastic plasmacytoid dendritic cell ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04216524

Study Details | NCT04216524 | Venetoclax, SL-401, and ... This phase II trial studies how well venetoclax, SL-401, and chemotherapy works in treating patients with blastic plasmacytoid dendritic cell neoplasm.

9. mdpi.com mdpi.com/1422-0067/25/3/1454

Breakthrough in Blastic Plasmacytoid Dendritic Cell ... BPDCN is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors.