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Venetoclax in Treating Participants With Recurrent or Refractory Mature T-Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03534180
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : September 24, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

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

Condition or disease Intervention/treatment Phase
Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Other: Laboratory Biomarker Analysis Drug: Venetoclax Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of venetoclax, including the dose ramp-up, in adults with relapsed or refractory mature T-cell lymphoma. (Safety Lead-in) II. To estimate the overall response rate (ORR) of venetoclax in patients with relapsed or refractory mature T-cell lymphoma. (Phase 2)

SECONDARY OBJECTIVES:

I. To evaluate the complete response rate, duration of response, time to response, overall survival and progression free survival of venetoclax in relapsed/refractory mature T-cell lymphoma. (Phase 2) II. To further characterize the safety and toxicities of venetoclax in relapsed/refractory mature T-cell lymphoma. (Phase 2)

EXPLORATORY OBJECTIVES:

I. 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.

Participants receive venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up periodically for up to 24 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Venetoclax With Safety Lead-In for Treatment of Relapsed/Refractory Mature T-Cell Lymphomas
Actual Study Start Date : September 11, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Venetoclax

Arm Intervention/treatment
Experimental: Treatment (venetoclax)
Participants receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Venetoclax
Given PO
Other Names:
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta




Primary Outcome Measures :
  1. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 [ Time Frame: Up to 30 days post-treatment ]
    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.

  2. Overall response rate (ORR) assessed by Lugano Classification 2014 (Phase II) [ Time Frame: Up to 24 months ]
    ORR includes the proportion of patients achieving completion response (CR) or partial response (PR). Rates and 95% Clopper-Pearson binomial confidence interval (CI) will be calculated for overall response rate. The response evaluation will be based on a Simon's Two-Stage Optimal design to distinguish a promising 30% response rate (alternative hypothesis) from a disappointing rate (null hypothesis) of 10%, at a one-sided type I error of 10% and a power of 80%.


Secondary Outcome Measures :
  1. Complete response rate (CR) defined using by Lugano Classification 2014 [ Time Frame: Up to 24 months ]
    Rates and 95% Clopper-Pearson binomial confidence interval (CI) will be calculated for overall response rate (patients that have confirmed CR or PR), as well as for CR rate. The response evaluation will be based on a Simon's Two-Stage Optimal design to distinguish a promising 30% response rate (alternative hypothesis) from a disappointing rate (null hypothesis) of 10%, at a one-sided type I error of 10% and a power of 80%.

  2. Duration of response (DOR) assessed using Lugano Classification 2014 [ Time Frame: From the start of study treatment up to 24 months ]
    DOR will be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error.

  3. Progression-free survival (PFS) [ Time Frame: From the start of study treatment up to 24 months ]
    PFS to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error. Median progression-free survival and overall survival and their corresponding 95% CIs will be estimated.

  4. Overall survival (OS) [ Time Frame: From the start of study treatment up to 24 months ]
    OS to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error. Median progression-free survival and overall survival and their corresponding 95% CIs will be estimated.

  5. Time to response (TTR) assessed by Lugano Classification 2014 [ Time Frame: From the start of study treatment up to 24 months ]
    TTR to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error.


Other Outcome Measures:
  1. Change in Bcl-2 gene expression [ Time Frame: At baseline and during course 1 or 2 (each course is 28 days) ]
    Tumor tissue samples will be collected from participants for assessment. Summary statistics and plots will be used to describe the pre- and post-treatment gene expression levels and the associated change between the timepoints. Paired t-test or Wilcoxon signed rank test will be used to explore the difference in gene expression levels before and after treatment. Data transformation such as log transformation will be considered if appropriate. For the exploratory correlation of these gene expression level/change with response, analyses comparing groups of participants defined by response may be conducted by two-sample t-test or Wilcoxon rank sum test. For the exploratory correlation of these endpoints with survival outcomes, survival analysis techniques such as Log rank test will be used.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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)
  • To be performed within 14 days prior to day 1 of protocol therapy: absolute neutrophil count (ANC) >= 1,000/mm^3

    • 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
  • To be performed within 14 days prior to day 1 of protocol therapy: platelets >= 30,000/mm^3 * 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

  • To be performed within 14 days prior to day 1 of protocol therapy: total bilirubin =< 1.5 x upper limit of normal (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 * If hepatic involvement by lymphoma: AST =< 5 x ULN
  • To be performed within 14 days prior to day 1 of protocol therapy: alanine aminotransferase (ALT) =< 3 x ULN

    * If hepatic involvement by lymphoma: ALT =< 5 x ULN

  • To be performed within 14 days prior to day 1 of protocol therapy: creatinine clearance of >= 50 mL/min per 24 hour urine or the Cockcroft-Gault formula
  • 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)

Exclusion Criteria:

  • 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 3 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)
  • A history of prior significant toxicity, other than thrombocytopenia, from another Bcl-2 family protein inhibitor
  • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03534180


Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Jasmine M. Zain, MD    626-256-4673 ext 82405    jazain@coh.org   
Principal Investigator: Jasmine M. Zain, MD         
United States, Missouri
Washington University School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jasmine M. Zain    626-256-4673 ext 82405    jazain@coh.org   
Principal Investigator: Neha Mehta-Shah         
United States, Nebraska
University of Nebraska Medical Center Not yet recruiting
Omaha, Nebraska, United States, 68198
Contact: Jasmine M. Zain    626-256-4673 ext 82405    jazain@coh.org   
Principal Investigator: Matthew A. Lunning         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jasmine Zain City of Hope Medical Center

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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03534180     History of Changes
Other Study ID Numbers: 18119
NCI-2018-00810 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
18119 ( Other Identifier: City of Hope Medical Center )
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: September 24, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Venetoclax
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents