Venetoclax for Blastic Plasmacytoid Dendritic Cell Neoplasm

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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a drug as a possible treatment for BPDCN. The intervention involved in this study is: Venetoclax

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.

What data supports the effectiveness of the drug Venetoclax for treating Blastic Plasmacytoid Dendritic Cell Neoplasm?

Venetoclax has shown effectiveness in treating a type of blood cancer called multiple myeloma, particularly in patients with a specific genetic marker (t(11;14)). In these patients, a high percentage experienced significant improvement, suggesting potential benefits for similar blood-related conditions. ^{1 2 3 4 5}

What makes the drug Venetoclax unique for treating Blastic Plasmacytoid Dendritic Cell Neoplasm?

Venetoclax is unique because it is a selective inhibitor of the B-cell lymphoma 2 (BCL-2) protein, which helps cancer cells survive. By blocking this protein, Venetoclax can restore the natural process of cell death in cancer cells, making it a novel option for treating various blood cancers, even though there are no standard treatments specifically for Blastic Plasmacytoid Dendritic Cell Neoplasm. ^{6 7 8 9 10}

Research Team

Andrew Lane, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

References

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

Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis. [2021]

2. United States 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. [2017]

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

Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. [2017]

4. Germany pubmed.ncbi.nlm.nih.gov

A dose regimen-finding study to evaluate the safety, tolerability, pharmacokinetics, and activity of oratecan in subjects with advanced malignancies. [2022]

5. United States 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. [2017]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. [2018]

8. Cyprus pubmed.ncbi.nlm.nih.gov

Combination of Venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia: A case series from a single center. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[Research Advance of Venetoclax in Hematological Tumors--Review]. [2020]

10. United States 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). [2022]