Anaplastic Large Cell LymphomaPhase 2NCT03534180
Venetoclax and Romidepsin in Treating Patients With Recurrent or Refractory Mature T-Cell Lymphoma
A Phase 2 study testing Laboratory Biomarker Analysis, Romidepsin and Venetoclax in people with Anaplastic Large Cell Lymphoma and Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, run by City of Hope Medical Center at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Large Cell Lymphoma, Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
- What is being tested?
- Laboratory Biomarker Analysis, Romidepsin and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Aug 2018to 26 Jul 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Platelets >= 30,000/mm^3 (to be performed within 14 days prior to day 1 of protocol therapy)
- NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
- Exception: Unless documented bone marrow involvement by lymphoma
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (=< 3 x ULN for Gilbert's syndrome or documented hepatic involvement by lymphoma) (to be performed within 14 days prior to day 1 of protocol therapy)
- Aspartate aminotransferase (AST) =< 3 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)
- If hepatic involvement by lymphoma: AST =< 5 x ULN
- Alanine aminotransferase (ALT) =< 3 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)
- If hepatic involvement by lymphoma: ALT =< 5 x ULN
- Creatinine clearance of >= 50 mL/min per 24 hour urine or the Cockcroft-Gault formula (to be performed within 14 days prior to day 1 of protocol therapy)
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by WOCBP and males of childbearing potential* to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 90 days after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Who cannot join
- 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
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- 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:
- Congenital long QT syndrome
- QTc (corrected QT interval on electrocardiogram [ECG]) interval > 480 milliseconds
- Any cardiac arrhythmia requiring anti-arrhythmic medication
- Patients with a history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest, unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
- Active infection requiring systemic therapy
- Unable to swallow capsules, has a partial or small bowel obstruction, or has a gastrointestinal condition resulting in a malabsorptive syndrome (e.g. small bowel resection with malabsorption)
- WOCBP: Pregnant or breastfeeding
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope Medical Center
Duarte, California, 91010
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: A Phase 2 Study of Venetoclax and Romidepsin With Safety Lead-In for Treatment of Relapsed/Refractory Mature T-Cell Lymphomas
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability of the combination of venetoclax with romidepsin, including the dose ramp-up, in adults with relapsed or refractory mature T-cell lymphoma. (Safety Lead-in) II. To estimate the efficacy as measured by the overall response rate (ORR) of venetoclax in patients with relapsed or refractory mature T-cell lymphoma. (Phase 2)
SECONDARY OBJECTIVES:
- To evaluate the complete response rate, duration of response, time to response, overall survival and progression free survival associated with venetoclax and romidepsin in relapsed/refractory mature T-cell lymphoma. (Phase 2) II. To further characterize the safety and toxicities of venetoclax and romidepsin combination in relapsed/refractory mature T-cell lymphoma. (Phase 2)
EXPLORATORY OBJECTIVES:
- To determine BCL2 protein expression in base line treatment tumor samples and correlatieon with response.
II. To determine changes in Bcl-2 gene expression in pre- and post-treatment tumor samples of mature T- cell lymphoma.
OUTLINE: This is a safety lead-in dose-escalation study, followed by a phase II study.
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 and romidepsin intravenously (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.
After completion of study treatment, patients are followed up periodically for up to 24 months.
- 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
- Being tested
- Laboratory Biomarker Analysis, Romidepsin, Venetoclax
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
RomidepsinDrug
Also called Antibiotic FR 901228, Depsipeptide, FK228, FR901228
Given IV
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Laboratory Biomarker Analysis; Drug: Romidepsin; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 days post-treatment, an average of 4 months.
Secondary outcomes (1)
Overall Survival at 100 Days
Overall survival (OS) was measured from start of the study treatment to death from any cause. OS to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error.
Measured: From the start of study treatment up to 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start21 Aug 2018
- Primary completion21 Apr 2021
- Study completion26 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anaplastic Large Cell LymphomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jasmine M Zain, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03534180
- Sponsor's protocol ID
- 18119
- Other IDs
- NCI-2018-00810, 18119, P30CA033572
- Status last verified
- Oct 2023
- First submitted
- 9 May 2018
- Last updated
- 19 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Venetoclax and Romidepsin With Safety Lead-In for Treatment of Relapsed/Refractory Mature T-Cell Lymphomas
- ClinicalTrials.gov ID
- NCT03534180
- Acronym / sponsor ID
- 18119
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 21 Aug 2018 (actual)
- Primary completion
- 21 Apr 2021 (actual)
- Study completion
- 26 Jul 2023 (actual)
- First posted
- 23 May 2018 (actual)
- Results
- Posted 22 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability of the combination of venetoclax with romidepsin, including the dose ramp-up, in adults with relapsed or refractory mature T-cell lymphoma. (Safety Lead-in) II. To estimate the efficacy as measured by the overall response rate (ORR) of venetoclax in patients with relapsed or refractory mature T-cell lymphoma. (Phase 2)
SECONDARY OBJECTIVES:
- To evaluate the complete response rate, duration of response, time to response, overall survival and progression free survival associated with venetoclax and romidepsin in relapsed/refractory mature T-cell lymphoma. (Phase 2) II. To further characterize the safety and toxicities of venetoclax and romidepsin combination in relapsed/refractory mature T-cell lymphoma. (Phase 2)
EXPLORATORY OBJECTIVES:
- To determine BCL2 protein expression in base line treatment tumor samples and correlatieon with response.
II. To determine changes in Bcl-2 gene expression in pre- and post-treatment tumor samples of mature T- cell lymphoma.
OUTLINE: This is a safety lead-in dose-escalation study, followed by a phase II study.
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 and romidepsin intravenously (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.
After completion of study treatment, patients are followed up periodically for up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (venetoclax, romidepsin) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Romidepsin, Drug: VenetoclaxPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (venetoclax, romidepsin) |
| RomidepsinAlso: Antibiotic FR 901228, Depsipeptide, FK228, FR901228Given IV | Drug | Treatment (venetoclax, romidepsin) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (venetoclax, romidepsin) |
Primary outcome
Number of Patients With Grade 3 or Above Toxicities
Time frame: Up to 30 days post-treatment, an average of 4 months.
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.
1 secondary outcome
Overall Survival at 100 Days
Time frame: From the start of study treatment up to 100 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jasmine M Zain principal investigator
City of Hope Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Romidepsin and Venetoclax in people with Anaplastic Large Cell Lymphoma and Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, run by City of Hope Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Grade 3 or Above Toxicities (time frame: Up to 30 days post-treatment, an average of 4 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2023.