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Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors

Primary Purpose

Recurrent Classic Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Brentuximab Vedotin
Hematopoietic Cell Transplantation
Nivolumab
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Classic Hodgkin Lymphoma

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed classical Hodgkin lymphoma
  • Patients must be 12 years of age or older
  • Patients must have received at least 1-2 prior multi-agent chemotherapy or immunotherapy regimens will be divided into two cohorts based on the following clinical scenarios:

    • Patients enrolled to cohort A must have received only ONE prior brentuximab-containing regimen with NO prior checkpoint inhibitors. Patients enrolled to cohort A must have received brentuximab as part of their first-line treatment regimen.
    • Patients enrolled to cohort B must have received only ONE prior immune checkpoint inhibitor- (i.e. nivolumab or pembrolizumab) containing regimen and NO prior brentuximab. Patients in cohort B may have received an immune checkpoint inhibitor during either their first- or second-line treatment regimen.
    • If radiation is used as part of the planned front-line treatment regimen (i.e., brentuximab vedotin-doxorubicin-vinblastine-dacarbazine [BV-AVD] + radiation therapy [RT] for bulky stage II disease), this will count as only 1 prior therapy. Additionally, radiation as consolidation after a second-line multi-agent chemotherapy regimen is permitted and will not be counted as a third regimen
  • No prior autologous or allogeneic transplant
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 for patients > 18 years old, or Lansky performance status of >= 50 for patients ages 12-18 years
  • Enrolling patients must have measurable disease defined as a tumor or nodal mass > 1.5 cm in at least one dimension
  • Resolution of all prior toxicities, including peripheral neuropathy, to a =< grade 1
  • Absolute neutrophil count (ANC) >= 750, unless disease related (within 28 days of cycle 1 day 1)
  • Platelets >= 50,000, unless disease related (within 28 days of cycle 1 day 1)
  • Creatinine =< upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 3 x ULN (within 28 days of cycle 1 day 1)
  • Bilirubin =< 2 mg/dL (within 28 days of cycle 1 day 1)
  • Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with HIV infection must meet the following criteria: No evidence of co-infection with hepatitis B or C; CD4+ count >= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL. Patients with HIV must have ongoing follow-up with an infectious disease specialist and must have been evaluated within 90 days of cycle 1 day 1.
  • Females of child-bearing potential (FCBP) must have a negative urine pregnancy test prior to starting therapy. If the test is positive, pregnancy must be ruled out
  • FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation, and 6 months after completion of brentuximab and/or nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

    • A female of childbearing potential (FCBP) is a post-menarcheal woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
  • Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer >= 2 weeks before the start of study therapy
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
  • Evidence of a personally signed informed consent by patients >= 18 year old (YO) or parent or legally authorized representative (LAR) for patients 12-17 YO indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. Patients 12-17 will also be required to give assent to the process per institutional guidelines

Exclusion Criteria:

  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for >= 2 years or which will not limit survival to < 2 years
  • Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events to =< grade 1
  • Active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, interstitial lung disease, and colitis
  • Active central nervous system (CNS) involvement with lymphoma
  • Patients with hepatitis B (positive hepatitis B virus surface antigen [HBsAg] or hepatitis B virus core antibody [HBcAb]) and those with positive hepatitis C virus (HCV) antibodies are not permitted to enroll
  • No active infection, or other active illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sites / Locations

  • Emory University Hospital/Winship Cancer InstituteRecruiting
  • Emory Saint Joseph's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (brentuximab vedotin, nivolumab)

Arm Description

Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Assessed per Lugano 2014 Criteria at any time point while on study therapy. Will be analyzed independently for each cohort (A and B).

Secondary Outcome Measures

Complete response rate (CRR)
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Will be determined per Lugano 2014 criteria at any disease assessment time point while the patient is receiving study therapy.
Progression-free survival (PFS)
Will be described using the Kaplan-Meier methodology. 95% confidence intervals for 1-year and 2-year PFS will be calculated, with standard errors estimated using the Greenwood formula. Patients alive without disease progression will be censored at last follow-up date.
Overall survival (OS)
Will be described using the Kaplan-Meier methodology. 95% confidence intervals for 1-year and 2-year OS will be calculated, with standard errors estimated using the Greenwood formula. Patients who have not died will be censored at last follow-up date.
Incidence of adverse events
According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
Incidence of symptomatic toxicity
Evaluated by Patient Reported Outcomes (PRO)-CTCAE or Pediatric PRO-CTCAE.

Full Information

First Posted
August 30, 2021
Last Updated
June 21, 2023
Sponsor
Emory University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05039073
Brief Title
Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors
Official Title
A Phase 2 Study of Brentuximab Vedotin Plus Nivolumab in Patients With Relapsed/Refractory Hodgkin Lymphoma Previously Treated With Brentuximab or Checkpoint Inhibitors
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2, 2022 (Actual)
Primary Completion Date
November 30, 2026 (Anticipated)
Study Completion Date
November 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies the effect of brentuximab vedotin and nivolumab in treating patients with classic Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory) that have been previously treated with brentuximab vedotin or checkpoint inhibitors. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving brentuximab vedotin and nivolumab in combination may be an effective treatment in patients with relapsed or refractory classic Hodgkin lymphoma previously treated with brentuximab vedotin or checkpoint inhibitors.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) with brentuximab vedotin (brentuximab)/nivolumab used in combination in patients in patients previously treated with brentuximab in combination with standard chemotherapy for Hodgkin lymphoma (HL). II. To determine the ORR with brentuximab/nivolumab in combination in patients previously treated with checkpoint inhibitors alone or in combination with standard chemotherapy for HL. SECONDARY OBJECTIVES: I. To determine the complete response rate (CRR) and progression-free survival (PFS) with brentuximab/nivolumab in patients previously treated with brentuximab in combination with standard chemotherapy for HL. II. To determine the CRR and PFS with brentuximab/nivolumab in patients previously treated with checkpoint inhibitors alone or in combination with standard chemotherapy for HL. III. To evaluate safety of this regimen using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 (v 5.0). IV. To determine the tolerability of this regimen using patient-reported outcomes including Patient Reported Outcomes (PRO)-CTCAE or pediatric PRO-CTCAE, neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX]), and fatigue quality of life (QOL) by strata. V. To determine the number of patients who proceed to autologous or allogeneic hematopoietic stem cell transplantation (HSCT). VI. To determine the number of patients who successfully undergo stem cell collection among those planning to proceed to autologous HSCT. OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant. After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Classic Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Treatment (brentuximab vedotin, nivolumab)
Arm Type
Experimental
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Hematopoietic Cell Transplantation
Other Intervention Name(s)
HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation
Intervention Description
Undergo HSCT
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Assessed per Lugano 2014 Criteria at any time point while on study therapy. Will be analyzed independently for each cohort (A and B).
Time Frame
Up to 16 cycles (each cycle is 21 days)
Secondary Outcome Measure Information:
Title
Complete response rate (CRR)
Description
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Will be determined per Lugano 2014 criteria at any disease assessment time point while the patient is receiving study therapy.
Time Frame
Up to 16 cycles (each cycle is 21 days)
Title
Progression-free survival (PFS)
Description
Will be described using the Kaplan-Meier methodology. 95% confidence intervals for 1-year and 2-year PFS will be calculated, with standard errors estimated using the Greenwood formula. Patients alive without disease progression will be censored at last follow-up date.
Time Frame
From time of study enrollment until first documentation of progressive disease or death from any cause, assessed up to 5 years
Title
Overall survival (OS)
Description
Will be described using the Kaplan-Meier methodology. 95% confidence intervals for 1-year and 2-year OS will be calculated, with standard errors estimated using the Greenwood formula. Patients who have not died will be censored at last follow-up date.
Time Frame
From time of study enrollment until death from any cause, assessed up to 5 years
Title
Incidence of adverse events
Description
According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
Time Frame
Up to 5 years
Title
Incidence of symptomatic toxicity
Description
Evaluated by Patient Reported Outcomes (PRO)-CTCAE or Pediatric PRO-CTCAE.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed classical Hodgkin lymphoma Patients must be 12 years of age or older Patients must have received at least 1-2 prior multi-agent chemotherapy or immunotherapy regimens will be divided into two cohorts based on the following clinical scenarios: Patients enrolled to cohort A must have received only ONE prior brentuximab-containing regimen with NO prior checkpoint inhibitors. Patients enrolled to cohort A must have received brentuximab as part of their first-line treatment regimen. Patients enrolled to cohort B must have received only ONE prior immune checkpoint inhibitor- (i.e. nivolumab or pembrolizumab) containing regimen and NO prior brentuximab. Patients in cohort B may have received an immune checkpoint inhibitor during either their first- or second-line treatment regimen. If radiation is used as part of the planned front-line treatment regimen (i.e., brentuximab vedotin-doxorubicin-vinblastine-dacarbazine [BV-AVD] + radiation therapy [RT] for bulky stage II disease), this will count as only 1 prior therapy. Additionally, radiation as consolidation after a second-line multi-agent chemotherapy regimen is permitted and will not be counted as a third regimen No prior autologous or allogeneic transplant Eastern Cooperative Oncology Group (ECOG) performance status =< 2 for patients > 18 years old, or Lansky performance status of >= 50 for patients ages 12-18 years Enrolling patients must have measurable disease defined as a tumor or nodal mass > 1.5 cm in at least one dimension Resolution of all prior toxicities, including peripheral neuropathy, to a =< grade 1 Absolute neutrophil count (ANC) >= 750, unless disease related (within 28 days of cycle 1 day 1) Platelets >= 50,000, unless disease related (within 28 days of cycle 1 day 1) Creatinine =< upper limit of normal (ULN) (within 28 days of cycle 1 day 1) Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 3 x ULN (within 28 days of cycle 1 day 1) Bilirubin =< 2 mg/dL (within 28 days of cycle 1 day 1) Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with HIV infection must meet the following criteria: No evidence of co-infection with hepatitis B or C; CD4+ count >= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL. Patients with HIV must have ongoing follow-up with an infectious disease specialist and must have been evaluated within 90 days of cycle 1 day 1. Females of child-bearing potential (FCBP) must have a negative urine pregnancy test prior to starting therapy. If the test is positive, pregnancy must be ruled out FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation, and 6 months after completion of brentuximab and/or nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A female of childbearing potential (FCBP) is a post-menarcheal woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer >= 2 weeks before the start of study therapy Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions Evidence of a personally signed informed consent by patients >= 18 year old (YO) or parent or legally authorized representative (LAR) for patients 12-17 YO indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. Patients 12-17 will also be required to give assent to the process per institutional guidelines Exclusion Criteria: Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for >= 2 years or which will not limit survival to < 2 years Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events to =< grade 1 Active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, interstitial lung disease, and colitis Active central nervous system (CNS) involvement with lymphoma Patients with hepatitis B (positive hepatitis B virus surface antigen [HBsAg] or hepatitis B virus core antibody [HBcAb]) and those with positive hepatitis C virus (HCV) antibodies are not permitted to enroll No active infection, or other active illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason T Romancik, MD
Organizational Affiliation
Emory University Hospital/Winship Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristie A. Blum
Phone
404-778-5933
Email
kablum@emory.edu
First Name & Middle Initial & Last Name & Degree
Blair Dykeman
Email
blair.dykeman@emory.edu
First Name & Middle Initial & Last Name & Degree
Jason T Romancik
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcela Algave, CRN
Phone
678-843-7544
Email
marcela.rodrigues.algave@emory.edu
First Name & Middle Initial & Last Name & Degree
Jason T Romancik, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors

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