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Leflunomide for the Treatment of Relapsed or Refractory CD30+ Lymphoproliferative Disorders

Primary Purpose

Recurrent Lymphoproliferative Disorder, Refractory Lymphoproliferative Disorder

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Leflunomide
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Lymphoproliferative Disorder

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative

    • Assent, when appropriate, will be obtained per institutional guidelines
  • Patients must have a life expectancy of > 3 months
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Patients must have a diagnosis of cutaneous CD30+ LYPD
  • Patients must be relapsed or are refractory to at least 1 prior line of therapy
  • At least 2 weeks from prior therapy to time of start of treatment. Prior therapy includes steroids (except prednisone or equivalent - up to 10 mg/day is allowed)
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (within 21 days prior to day 1 of protocol therapy). NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • Platelets >= 50,000/mm^3 (within 21 days prior to day 1 of protocol therapy). NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (within 21 days prior to day 1 of protocol therapy)
  • Aspartate aminotransferase (AST) =< 2.0 x ULN (within 21 days prior to Day 1 of protocol therapy)
  • Alanine aminotransferase (ALT) =< 2.0 x ULN (within 21 days prior to day 1 of protocol therapy)
  • Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 21 days prior to day 1 of protocol therapy)
  • Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (within 21 days prior to day 1 of protocol therapy)

    • If positive, hepatitis C RNA quantitation must be performed
  • Meets other institutional and federal requirements for infectious disease titer requirements. Note infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Negative for tuberculosis antigen (e.g. T-Spot test)
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 21 days prior to day 1 of protocol therapy). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control (hormonal or barrier method of birth control or abstinence) or abstain from heterosexual activity for the course of the study through at least three months after the last dose of protocol therapy. The effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 2 years (women only)

Exclusion Criteria:

  • Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period
  • Current or planned growth factor or transfusion support. If growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
  • Prior allogeneic transplant
  • Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
  • Known history of hepatitis B or hepatitis C infection
  • Known HIV infection
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide or cholestyramine
  • Non-hematologic malignancy within the past 3 years aside from the following exceptions:

    • Adequately treated basal cell or squamous cell skin cancer
    • Carcinoma in situ of the cervix
    • Prostate cancer < Gleason grade 6 with a stable prostate specific antigen (PSA)
    • Successfully treated in situ carcinoma of the breast
  • Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent
  • Pregnant women and women who are lactating. Leflunomide has potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is enrolled on this study
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc
  • 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)

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (leflunomide)

Arm Description

Patients receive leflunomide PO QD on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall response rate
Defined as the proportion of patients with a documented response (complete response [CR] or partial [PR]) any time during study treatment. Response will be categorized by modified severity weighted assessment tool (mSWAT). Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.

Secondary Outcome Measures

Complete response rate
Defined as the proportion of patients with a documented CR any time during study treatment. Response will be assessed by mSWAT. Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.
Duration of response
Will be calculated using Kaplan-Meier product limit estimator; median duration of response will also be estimated when possible.
Incidence of adverse events
Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized, in terms of type, grade, time of onset, duration, and attribution to the study treatment.

Full Information

First Posted
July 6, 2020
Last Updated
September 26, 2022
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04463615
Brief Title
Leflunomide for the Treatment of Relapsed or Refractory CD30+ Lymphoproliferative Disorders
Official Title
Pilot Trial of Leflunomide in Patients With CD30+ Lymphoproliferative Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 5, 2021 (Actual)
Primary Completion Date
July 16, 2023 (Anticipated)
Study Completion Date
July 16, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This trial studies how well leflunomide works for the treatment of patients with CD30+ lymphoproliferative disorders that have come back (relapsed) or do not respond to treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate overall response rate of leflunomide treatment. SECONDARY OBJECTIVES: I. To assess complete response rate and duration of response of leflunomide treatment. II. To assess toxicities of leflunomide treatment. III. To assess disease status by the CAILS (composite assessment of index lesion severity). EXPLORATORY OBJECTIVE: I. To generate a preliminary ribonucleic acid (RNA) signature associated with response of CD30+ lymphoproliferative disorders (LYPDs) cells to leflunomide. OUTLINE: Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Lymphoproliferative Disorder, Refractory Lymphoproliferative Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (leflunomide)
Arm Type
Experimental
Arm Description
Patients receive leflunomide PO QD on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Leflunomide
Other Intervention Name(s)
Arava, SU101
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Overall response rate
Description
Defined as the proportion of patients with a documented response (complete response [CR] or partial [PR]) any time during study treatment. Response will be categorized by modified severity weighted assessment tool (mSWAT). Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.
Time Frame
Up to 12 months post treatment
Secondary Outcome Measure Information:
Title
Complete response rate
Description
Defined as the proportion of patients with a documented CR any time during study treatment. Response will be assessed by mSWAT. Will be calculated along with the Clopper Pearson binomial 95% exact confidence intervals.
Time Frame
Up to 12 months post treatment
Title
Duration of response
Description
Will be calculated using Kaplan-Meier product limit estimator; median duration of response will also be estimated when possible.
Time Frame
Up to 12 months post treatment
Title
Incidence of adverse events
Description
Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized, in terms of type, grade, time of onset, duration, and attribution to the study treatment.
Time Frame
From the date of first documented response (CR or PR) to the first documented disease progression or death, whichever occurs first, assessed up to 12 months
Other Pre-specified Outcome Measures:
Title
Micro (mi)R ribonucleic acid (RNA)/messenger (m)RNA expression profile
Description
Data will be summarized by descriptive statistics. The data will also be used to explore the miRNA/mRNA that show significant differences between responders and non-responders after leflunomide treatment. For miRNA/RNA profiling, fold changes > 3 with an false discovery rate (FDR) < 0.05 will be considered significant.
Time Frame
Up to 12 months post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented informed consent of the participant and/or legally authorized representative Assent, when appropriate, will be obtained per institutional guidelines Patients must have a life expectancy of > 3 months Eastern Cooperative Oncology Group (ECOG) =< 2 Patients must have a diagnosis of cutaneous CD30+ LYPD Patients must be relapsed or are refractory to at least 1 prior line of therapy At least 2 weeks from prior therapy to time of start of treatment. Prior therapy includes steroids (except prednisone or equivalent - up to 10 mg/day is allowed) Absolute neutrophil count (ANC) >= 1000/mm^3 (within 21 days prior to day 1 of protocol therapy). NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement Platelets >= 50,000/mm^3 (within 21 days prior to day 1 of protocol therapy). NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (within 21 days prior to day 1 of protocol therapy) Aspartate aminotransferase (AST) =< 2.0 x ULN (within 21 days prior to Day 1 of protocol therapy) Alanine aminotransferase (ALT) =< 2.0 x ULN (within 21 days prior to day 1 of protocol therapy) Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 21 days prior to day 1 of protocol therapy) Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (within 21 days prior to day 1 of protocol therapy) If positive, hepatitis C RNA quantitation must be performed Meets other institutional and federal requirements for infectious disease titer requirements. Note infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy Negative for tuberculosis antigen (e.g. T-Spot test) Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 21 days prior to day 1 of protocol therapy). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required Agreement by females and males of childbearing potential* to use an effective method of birth control (hormonal or barrier method of birth control or abstinence) or abstain from heterosexual activity for the course of the study through at least three months after the last dose of protocol therapy. The effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 2 years (women only) Exclusion Criteria: Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period Current or planned growth factor or transfusion support. If growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible Prior allogeneic transplant Acute active infection requiring systemic therapy within 2 weeks prior to enrollment Known history of hepatitis B or hepatitis C infection Known HIV infection History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide or cholestyramine Non-hematologic malignancy within the past 3 years aside from the following exceptions: Adequately treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix Prostate cancer < Gleason grade 6 with a stable prostate specific antigen (PSA) Successfully treated in situ carcinoma of the breast Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent Pregnant women and women who are lactating. Leflunomide has potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is enrolled on this study Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Farah R Abdulla
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Leflunomide for the Treatment of Relapsed or Refractory CD30+ Lymphoproliferative Disorders

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