- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04216524
Venetoclax, SL-401, and Chemotherapy for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm
Phase 2 Clinical Trial for Comprehensive Treatment Program for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Tagraxofusp (SL-401) in Combination With HCVAD/Mini-CVD and VENETOCLAX
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate progression-free survival (PFS) at 12 months of venetoclax (VEN) in combination with chemotherapy and SL-401 (tagraxofusp [TAG]) in patients with newly diagnosed blastic plasmacytoid dendritic cell neoplasm (BPDCN).
SECONDARY OBJECTIVES:
I. To determine the safety of the SL-401 in combination with VEN and in combination with chemotherapy in patients with newly diagnosed BPDCN by toxicity and futility monitoring.
II. To determine the efficacy by measurement of progression free survival (PFS), overall response rate (ORR): complete response (CR) and complete response with incomplete marrow recovery (CRi), clinical complete response (CRc) and remission duration of SL-401 in combination with chemotherapy and VEN in patients with newly diagnosed BPDCN.
III. To determine the rate of stem cell translant (SCT) within the first 8 cycles (understanding that some patients won't get SCT) in patients with newly diagnosed BPDCN.
EXPLORATORY OBJECTIVES:
I. To examine expression and function of BCL-2 family proteins and its modulation by VEN in BPDCN blasts.
II. To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR/CRi/CRc and its correlation with disease-free survival (DFS) and overall survival (OS).
III. To determine CD123 levels pre- and post-therapy. IV. To determine molecular mutations pre-and post- therapy as part of 81-gene panel by next-generation sequencing.
OUTLINE:
INDUCTION:
CYCLE 1: Patients receive tagraxofusp-erzs (SL-401) intravenously (IV) once daily (QD) over 15 minutes on days 1-5.
CYCLES 2, 4, 6, and 8: Patients receive tagraxofusp-erzs IV QD over 15 minutes on days 1-5, and venetoclax orally (PO) QD on days 1-14 of cycle 2, and days 1-7 of cycles 4, 6, and 8.
CYCLES 3 and 7: Patients receive venetoclax PO QD on days 1-7. Patients whose age < 60 receive hyper-CVAD and age >= 60 receive mini-hyper-CVD. Patients may receive rituximab IV over 90 minutes on days 1 and 8, methotrexate intrathecally (IT) on day 2, and/or cytarabine IT on day 8. Patients also receive venetoclax PO QD on days 1-7.
HYPER-CVAD (AGE < 60): Patients receive cyclophosphamide IV over 3 hours every 12 hours (Q12H) on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone orally (PO) or IV over 30 minutes on days 1-4 and 11-14, and doxorubicin IV over 24 hours on day 4.
MINI-HYPER-CVD (AGE >= 60): Patients receive cyclophosphamide IV over 3 hour Q12H on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone PO or IV over 30 minutes on days 1-4 and 11-14.
CYCLE 5: Patients receive venetoclax PO QD on days 1-7. Patients who age < 60 receive MTX/AraC and age >= 60 receive mini-MTX/AraC. Patients may receive rituximab IV over 4-6 hours on days 1 and 8, cytarabine IT on day 5, and/or methotrexate IT on day 8.
MTX/ARAC (AGE < 60): Patients receive methotrexate IV over 24 hours on day 1, and cytarabine IV over 3 hours Q12H on days 2 and 3.
MINI-MTX/ARAC (AGE >= 60): Patients receive methotrexate IV over 24 hours on day 1, methylprednisolone IV over 2 hours Q12H on days 1-3, and cytarabine IV over 3 hours Q12H on days 2 and 3.
ALL CYCLES: Treatment repeats every 28 days for 8 cycles in the absence of disease progression and unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO QD on days 1-7, POMP chemotherapy during cycles 1-5, 7-11, and 13-17, and SL-401 IV QD on days 1-5 of cycles 6, 12, and 18. Treatment repeats every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity.
POMP: Patients receive mercaptopurine PO three time daily (TID) on days 1-28, vincristine IV over 15 minutes on day 1, prednisone PO QD on days 1-5, and methotrexate PO once weekly.
After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Naveen Pemmaraju
- Phone Number: 713-792-4956
- Email: npemmaraju@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Naveen Pemmaraju
- Phone Number: 713-792-4956
- Email: npemmaraju@mdanderson.org
-
Principal Investigator:
- Naveen Pemmaraju
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) per 2016 World Health Organization (WHO) criteria
Patients may have received emergent chemotherapy prior to study enrollment:
- One prior cycle of SL-401, or other BPDCN-directed therapy, will be allowed prior to entering the study
- Prior or concomitant doses of aspacytarabine (ARA-C [cytarabine]) or hydroxyurea are allowed on before or during the study for proliferative disease due to BPDCN
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Albumin >= 3.2 g/dL (in the absence of receipt of intravenous albumin in the previous 72 hours)
- Serum creatinine < 1.5 x upper limit of normal (ULN)
- 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]).
- Ability to understand and the willingness to sign a written informed consent document
- Able to adhere to study visit schedule and other protocol requirements including follow-up for survival assessment
- Women of child-bearing potential and men enrolled on this protocol must agree to use adequate contraception for the duration of study participation and for 2 months after completion VEN administration. Acceptable birth control methods allowed to be used while on study include: Birth control pills or injections, intrauterine devices (IUDs), double-barrier methods for example condom in combination with spermicide. Males should not donate sperm while on study and for at least 8 weeks after the last dose of SL-401
- Left ventricular ejection fraction >= institutional lower limit of normal by multi-gated acquisition (MUGA) scan or echocardiogram within 30 days of first protocol treatment
Exclusion Criteria:
- Patient is pregnant or breastfeeding
- Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
- Major surgery or radiation therapy within 14 days prior to the first study dose
- Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and/or dexamethasone, or one dose of cytarabine) prior to starting therapy
- Symptomatic or untreated leptomeningeal disease or spinal cord compression
- Patients with active heart disease (New York Heart Association [NYHA] class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
- Prior treatment with VEN
- Malabsorption syndrome or other conditions that preclude enteral route of administration
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (SL-401, venetoclax, chemotherapy)
See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IT or IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IT, IV, or PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival (PFS)
Time Frame: Up to 6 years
|
The median PFS time will be estimated by Bayesian posterior estimates.
Estimated using the Kaplan-Meier method.
|
Up to 6 years
|
Incidence of adverse events
Time Frame: Up to 6 years
|
Will be reported by type, frequency and severity.
Highest toxicity grades per patient per course will be tabulated for selected adverse events and laboratory measurements.
|
Up to 6 years
|
Overall response rate
Time Frame: Up to 6 years
|
Overall response rate along with complete remission and complete remission with incomplete hematologic recovery will be estimated along with 95% confidence interval.
|
Up to 6 years
|
Rate of stem cell transplant
Time Frame: Up to 6 years
|
The response rate will be compared between subgroups (e.g.
minimal residual disease negativity, etc.) by Fisher's exact test, and Wilcoxon rank test will be used to compare the patient clinical information (e.g., protein expression) between subgroups such as response and non-response.
|
Up to 6 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Naveen Pemmaraju, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Neuroprotective Agents
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Dexamethasone
- Dexamethasone acetate
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
- BB 1101
- Cyclophosphamide
- Antibodies
- Immunoglobulins
- Venetoclax
- Rituximab
- Prednisone
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Cytarabine
- Methotrexate
- Vincristine
- Daunorubicin
- Mercaptopurine
- Cortisone
Other Study ID Numbers
- 2019-0587 (Other Identifier: M D Anderson Cancer Center)
- P30CA016672 (U.S. NIH Grant/Contract)
- NCI-2019-08358 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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