Venetoclax and Romidepsin in Treating Patients With Recurrent or Refractory Mature T-Cell Lymphoma

NCT03534180 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 18119NCI-2018-00810P30CA033572
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies the side effects and best dose of venetoclax and romidepsin to see how well it works in treating patients with mature T-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Venetoclax and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Anaplastic Large Cell Lymphoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Grade 3 or Above Toxicities

  Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. During the first 2 cycles, all grades of toxicity will be collected. After cycle 2, only the highest grade of any toxicity will be collected for each cycle during protocol treatment and for the period of safety follow-up after end of treatment.

  Up to 30 days post-treatment, an average of 4 months.

Secondary Outcomes (1)

• Overall Survival at 100 Days

  From the start of study treatment up to 100 days

Study Arms (1)

Treatment (venetoclax, romidepsin)

EXPERIMENTAL

Patients receive venetoclax PO QD on days 1-28 and romidepsin IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Romidepsin; Drug: Venetoclax

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (venetoclax, romidepsin)

Romidepsin DRUG

Given IV

Also known as: Antibiotic FR 901228, Depsipeptide, FK228, FR901228, Istodax, N-[(3S,4E)-3-Hydroxy-7-mercapto-1-oxo-4-heptenyl]-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoyl-L-valine, (4->1) Lactone, Cyclic

Treatment (venetoclax, romidepsin)

Venetoclax DRUG

Given PO

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

Treatment (venetoclax, romidepsin)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or the legally authorized representative
• Be willing to provide tissue
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Resolution of all acute toxic effects of prior therapy or surgical procedures to Common Terminology Criteria for Adverse Events (CTCAE) grade =\< 1 (except alopecia)
• Failed at least 2 prior systemic therapies. For anaplastic large cell lymphoma (ALCL) histologies this must include failure or intolerable side effects of brentuximab vedotin
• Histologically confirmed peripheral T-cell lymphoma (PTCL) as defined by the World Health Organization (WHO) criteria 2016, excluding cutaneous T-cell lymphoma (CTCL); transformed mycosis fungoides is allowed
• Measurable disease defined as:
• Computed tomography (CT)/magnetic resonance imaging (MRI)/ or positron emission tomography (PET) scan, with at least one nodal site of disease which is 1.5 cm in longest dimension, and/or spleen \> 13 cm in vertical length, and/or diffuse enlargement of liver with or without focal nodules (Lugano 2014); extra nodal sites with biopsy proven abnormal lesions are allowed including skin
• Patients with only bone marrow involvement will be acceptable
• Prior stem cell transplant allowed
• If allogeneic hematopoietic cell transplantation (HCT) must have recovered from acute toxicity
• Cannot have active acute or chronic graft versus host disease (GvHD) and must be off immunosuppressive therapies
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy)
• NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• Exception: Unless documented bone marrow involvement by lymphoma

You may not qualify if:

• Bcl2 inhibitors
• Any systemic anti-lymphoma therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating protocol therapy
• Radiation and/or surgery (except lymph node or other diagnostic biopsies) within 14 days prior to day 1 of protocol therapy
• Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication within 7 days prior to day 1 of protocol therapy; stable ongoing corticosteroid use (i.e. at least 30 days) up to an equivalent dose of 20 mg of prednisone is permissible
• Strong or moderate CYP3A inhibitors within 7 days prior to day 1 of protocol therapy
• Strong or moderate CYP3A inducers within 7 days prior to day 1 of protocol therapy
• P-gp inhibitors within 7 days prior to day 1 of protocol therapy
• Narrow therapeutic index P-gp substrates within 7 days prior to day 1 of protocol therapy
• Any other investigational agent or used an investigational device within 21 days prior to day 1 of protocol therapy
• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
• Active human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who have an undetectable HIV viral load with CD4 \> 200 and are on highly active antiretroviral therapy (HAART) medication are allowed; subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded; patients who have had hepatitis C but have finished treatment and are PCR negative will be allowed (testing to be done only in patients suspected of having infections or exposures)
• Concurrent malignancy requiring active therapy
• Known central nervous system or meningeal involvement (in the absence of symptoms, investigation into central nervous system involvement is not required)
• Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions
• Patients with known cardiac abnormalities such as:

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell

Interventions

romidepsin; Depsipeptides; Lactones; 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

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals

Results Point of Contact

• Title: Dr. Jasmine Zain, MD
• Organization: City of Hope

jazain@coh.org

6263598111

Study Officials

• Jasmine M Zain

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: May 9, 2018
• First Posted: May 23, 2018
• Study Start: August 21, 2018
• Primary Completion: April 21, 2021
• Study Completion: July 26, 2023
• Last Updated: October 19, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-10

Locations

US (2)