Venetoclax and Eprenetapopt for the Treatment of Relapsed of Refractory Mantle Cell Lymphoma

NCT04990778 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-1325NCI-2021-05596
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial investigates the effect of venetoclax and eprenetapopt in treating patients with mantle cell lymphoma that has come back (relapsed) or dose not respond to treatment (refractory). Chemotherapy drugs, such as venetoclax and eprenetapopt, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (complete and partial responses)

  Will be based on Cheson, Lugano Classification 2014. Its associated exact 95% confidence interval will be presented.

  At 16 weeks

Secondary Outcomes (7)

• Complete response rate

  through study completion, an average of 1 year

• Progression free survival

  through study completion, an average of 1 year

• Duration of response (DOR)

  From the date of achieving earliest response (complete response or partial response) to the date this response is not maintained

• Overall survival

  From the date of treatment start to date of death or last follow up either on or off study

• Frequency of adverse events

  Up to study completion

Study Arms (1)

Treatment (eprenetapopt, venetoclax)

EXPERIMENTAL

Patients receive eprenetapopt IV over 6 hours on days 1-4 and venetoclax PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Eprenetapopt; Drug: Venetoclax

Interventions

Eprenetapopt DRUG

Given IV

Also known as: APR-246, PRIMA-1MET

Treatment (eprenetapopt, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (eprenetapopt, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of mantle cell lymphoma in tissue biopsy and chromosome translocation t(11;14), (q13;q32) and/or overexpress cyclin D1 in tissue biopsy, cyclin D1 negative MCL (confirmed by hematopathology's are allowed and blastoid/pleomorphic morphology, complex karyotype are allowed)
• Patients must have relapsed or refractory MCL (irrespective of prior BTK inhibitor or anti CD19 chimeric antigen receptor T cell \[CART\] exposure)
• Prior exposure to venetoclax is allowed as long as the patients had clear evidence of disease progression on venetoclax (alone or in combination with other therapy) and the maximum dose of venetoclax was =\< 400 mg. Doses \> 400 mg and progression on venetoclax are excluded
• Patients with known TP53 status (positive or negative) - confirmed by a pre-treatment biopsy a pre-treatment biopsy to be sent for TP53 sequencing and TP53 testing by fluorescence in situ hybridization (FISH) and TP53 by immunohistochemistry (IHC) from hem-path to the hem-pathology and get the TP53 status before starting the study as a part of screening. To send bone marrow (BM) for TP53 assessment if it is involved by MCL \> 10% instead
• TP53 mutation positive by IHC (\>= 50%) in MCL cells and/or TP53 deletion by FISH in bone marrow (BM) or in tissues and/or del17p in karyotype or TP53 deletion positive by FISH in BM/involved tissue with MCL or presence of somatic TP53 mutations by next generation sequencing (NGS) or whole exome sequencing (WES) and TP53 wild type or mutation-negative status are allowed
• High risk MCL (blastoid/pleomorphic histology, high Ki-67 \[\>= 50%\], TP53/NOTCH1/2, NSD2, CYCLIN D1, BIRC3 mutated, complex karyotype, Bulky disease \> 5 cm, FISH positive for TP53 or MYC from involved tissues, high risk Mantle Cell Lymphoma International Prognostic Index \[MIPI\] score)
• Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form
• Age from \>= 18 years at the time of signing the informed consent
• Patients must have bi-dimensional measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Absolute neutrophil count (ANC) \> 1,000/mm\^3
• If bone marrow and spleen are involved, the counts of ANC will not be limited
• Platelet count \>= 100,000/mm\^3
• If bone marrow and spleen are involved, the counts of platelets will not be limited
• Prothrombin time (or international normalized ratio) and partial thromboplastin time not to exceed 1.2 times the institution normal range (patients with an elevated prothrombin time and known lupus anticoagulant may be eligible for participation after consulting the medical monitor)

You may not qualify if:

• Known central nervous system (CNS) involvement by lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease (as shown by magnetic resonance imaging \[MRI\] brain and/or cerebrospinal fluid \[CSF\] or clinical exam by neurologists may be eligible if a compelling clinical rationale is provided to Aprea pharma which is the supporting company and the institution is the investigational new drug \[IND\] sponsor)
• Any serious uncontrolled medical condition including but not limited to, uncontrolled hypertension, diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active infection, active hemorrhage, laboratory abnormality, or psychiatric illness that places the patient at unacceptable risk and would prevent the subject from signing the informed consent form
• Pregnant or lactating females
• Known human immunodeficiency virus (HIV) infection
• Patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody. Active hepatitis B/C. Patients with prior exposure to hepatitis B (i.e. positive anti-hepatitis B CORE antibody) must demonstrate hepatitis B polymerase chain reaction (PCR) to be negative during screening period and undergo prophylaxis and monitoring for hepatitis B according to institutional guidelines. Known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal (GI) consultation
• Clinically significant cardiovascular diseases as determined after cardiology consultation, including uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months of screening or any class 3 (moderate) or 4 (severe) cardiac disease following the New York Heart Association classification, known left ventricular ejection fraction (LVEF) \< 40%, history of familial long QT syndrome, Symptomatic atrial or ventricular arrhythmias not controlled by medications. Otherwise, significant screening electrocardiogram (ECG) abnormalities and/or pacemaker may be allowed after discussion with the PI and the cardiologist clearance
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of venetoclax
• With known allergies to xanthine oxidase inhibitors and/or rasburicase
• 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 study treatment administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
• No concomitant anticancer therapies, immunotherapies, cellular, or radiotherapy. No major surgery within 3 weeks prior to first dose of study treatment. Washout period for chemotherapy is 14 days. Washout period for targeted agents is 2 weeks or 5 half-lives (t1/2) (whichever is shorter). Washout period for antibody-based immunotherapies or cellular therapies is 4 weeks. Washout period for radiotherapy is 7 days (limited field) and 28 days (extended field that includes BM). Washout period must be completed prior to any treatment administration
• Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia
• Consumption of grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting study treatment
• Concomitant steroids for disease related pain control are allowed at any dose but must be discontinued prior to any study treatment initiation. Chronic use of corticosteroids is allowed up to 20 mg prednisone daily for non-cancer related conditions at the time of study start
• History of allogeneic or autologous stem cell transplant (SCT) or CAR-T therapy within the last 30 days or with any of the following:
• Active uncontrolled graft versus host disease (GVHD)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

eprenetapopt; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Luhua (Michael) Wang

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 4, 2021
• Study Start: November 30, 2021
• Primary Completion: March 24, 2023
• Study Completion: March 24, 2023
• Last Updated: March 10, 2022

Record last verified: 2022-02

Locations

US (1)