40 Participants Needed

Venetoclax + Tagraxofusp-erzs + Chemotherapy for BPDCN

Naveen Pemmaraju | MD Anderson Cancer ...
Overseen ByNaveen Pemmaraju, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well venetoclax, SL-401, and chemotherapy works in treating patients with blastic plasmacytoid dendritic cell neoplasm. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. SL-401 is a recombinant protein consisting of IL-3 linked to a toxic agent called DT. IL-3 attaches to IL-3 receptors on tumor cells in a targeted way and delivers DT to kill them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and SL-401 with chemotherapy may be an effective treatment for patients with blastic plasmacytoid dendritic cell neoplasm.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it allows for certain medications like ARA-C (cytarabine) or Hydroxyurea to be used before or during the study for specific conditions related to BPDCN.

What data supports the effectiveness of the drugs used in the Venetoclax + Tagraxofusp-erzs + Chemotherapy for BPDCN trial?

The hyper-CVAD regimen, which includes cyclophosphamide, vincristine, doxorubicin, and dexamethasone, has shown significant activity in treating adult acute lymphocytic leukemia and other blood cancers. Additionally, the CyclOBEAP regimen, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, achieved a high complete response rate in patients with aggressive lymphoma, suggesting potential effectiveness of these drugs in similar blood-related conditions.12345

Is the combination of Venetoclax, Tagraxofusp-erzs, and chemotherapy generally safe for humans?

The safety of doxorubicin, a component of the chemotherapy regimen, has been studied in combination with other drugs, showing that it can be well-tolerated when administered properly. However, some studies have noted potential risks, such as cardiotoxicity (heart damage) and secondary cancers, when used with certain drugs like dexrazoxane. Overall, while these drugs have been used safely in various treatments, they can have significant side effects that need careful management.678910

What makes the drug combination of Venetoclax, Tagraxofusp-erzs, and Chemotherapy unique for BPDCN?

This drug combination is unique because it includes Venetoclax, which targets a specific protein (BCL-2) that helps cancer cells survive, and Tagraxofusp-erzs, which is a targeted therapy specifically designed for BPDCN (a rare type of blood cancer). This combination aims to enhance the effectiveness of traditional chemotherapy by using these targeted approaches.1011121314

Research Team

Naveen Pemmaraju | MD Anderson Cancer ...

Naveen Pemmaraju, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with a confirmed diagnosis of blastic plasmacytoid dendritic cell neoplasm. Participants should be in relatively good health (ECOG status 0-2), have normal heart function, and agree to use effective contraception. People who've had major surgery or certain treatments recently, are pregnant or breastfeeding, have active hepatitis B/C or HIV, severe heart issues, malabsorption syndrome, untreated brain/spinal cord problems, or prior venetoclax treatment can't join.

Inclusion Criteria

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
Total bilirubin < 1.5 x ULN (if total bilirubin is > 1.5 x but < 3 x ULN, and thought to be elevated due to Gilbert's disease or the patient's BPDCN, the subject may be eligible but must discuss with the principal investigator [PI])
I have taken or am taking ARA-C or hydroxyurea for BPDCN.
See 9 more

Exclusion Criteria

I haven't had chemotherapy, radiotherapy, or experimental treatments in the last 14 days, except for specific allowed medications.
I have previously been treated with VEN.
Patient is pregnant or breastfeeding
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive tagraxofusp-erzs (SL-401) and venetoclax with chemotherapy over multiple cycles

8 cycles (28 days each)
Multiple visits per cycle for drug administration

Maintenance

Patients receive venetoclax and POMP chemotherapy over 24 cycles

24 cycles (28 days each)
Regular visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years
Follow-up at 30 days, then every 3 months

Treatment Details

Interventions

  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Doxorubicin
  • Mercaptopurine
  • Methotrexate
  • Methylprednisolone
  • Prednisone
  • Rituximab
  • Tagraxofusp-erzs
  • Venetoclax
  • Vincristine
Trial OverviewThe study tests the effectiveness of combining venetoclax and SL-401 with standard chemotherapy in treating blastic plasmacytoid dendritic cell neoplasm. Venetoclax targets enzymes needed for tumor growth; SL-401 delivers a toxin directly to tumor cells via IL-3 receptors; chemotherapy aims to kill or stop cancer cells from growing and spreading.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (SL-401, venetoclax, chemotherapy)Experimental Treatment12 Interventions
See detailed description.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

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Approved in United States as Cytoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
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Approved in European Union as Endoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
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Approved in Canada as Neosar for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
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Approved in Japan as Endoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

The OEPA-COPDAC chemotherapy regimen, which replaces procarbazine with etoposide and dacarbazine, was found to be tolerable in terms of toxicity for boys with Hodgkin's lymphoma, with hematotoxicity being less pronounced compared to the traditional COPP regimen.
After a median follow-up of 58.6 months, the overall survival rate was 97.4% and the event-free survival rate was 89.0%, indicating that OEPA-COPDAC is as effective as the standard OPPA-COPP regimen for treating intermediate and advanced stages of classical Hodgkin's lymphoma in pediatric patients.
Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study.Mauz-KΓΆrholz, C., Hasenclever, D., DΓΆrffel, W., et al.[2022]
The CyclOBEAP regimen, which adds etoposide and bleomycin to a standard CHOP-like treatment, achieved an 88% complete response rate in 121 patients with aggressive lymphoma over a 12-week period, indicating its efficacy.
The 5-year overall survival rate was 72% and the progression-free survival rate was 62%, with no treatment-related deaths reported, suggesting that the regimen is safe while enhancing the effectiveness of traditional CHOP therapy.
Multicenter phase II study of the CyclOBEAP (CHOP-like + etoposide and bleomycin) regimen for patients with poor-prognosis aggressive lymphoma.Niitsu, N., Okamoto, M., Aoki, S., et al.[2015]
In a study of 42 children with newly diagnosed stage III or IV neuroblastoma, the OPEC chemotherapy regimen resulted in a good partial response in 74% of patients, with an even higher response rate of 78% among those who strictly followed the treatment protocol.
The OPEC regimen was found to be at least as effective as the more toxic OPEC-D regimen, with significantly lower treatment-related complications, suggesting it could be a safer alternative for treating advanced neuroblastoma.
Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.Shafford, EA., Rogers, DW., Pritchard, J.[2017]

References

Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. [2022]
Multicenter phase II study of the CyclOBEAP (CHOP-like + etoposide and bleomycin) regimen for patients with poor-prognosis aggressive lymphoma. [2015]
Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26. [2017]
The hyper-CVAD regimen in adult acute lymphocytic leukemia. [2019]
MOPPEBVCAD chemotherapy with limited and conditioned radiotherapy in advanced Hodgkin's lymphoma: 10-year results, late toxicity, and second tumors. [2015]
Efficacy and toxicity of liposomal daunorubicin included in PVABEC regimen for aggressive NHL of the elderly. [2019]
The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium. [2022]
Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. [2022]
Paclitaxel-based combination chemotherapy for breast cancer. [2015]
10.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[Cardioxane in pediatric oncohematology]. [2013]
[Survey of anthracyclines derivatives in haematology (author's transl)]. [2013]
12.United Statespubmed.ncbi.nlm.nih.gov
Overview and historical development of dexrazoxane. [2013]
13.United Statespubmed.ncbi.nlm.nih.gov
Synergistic activity of doxorubicin and the bisdioxopiperazine (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187) against the murine sarcoma S180 cell line. [2013]
14.United Statespubmed.ncbi.nlm.nih.gov
Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine). [2019]