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A Trial Comparing Chemotherapy Versus Novel Immune Checkpoint Inhibitor (Pembrolizumab) Plus Chemotherapy in Treating Relapsed/Refractory Classical Hodgkin Lymphoma
Randomized Phase III Trial of Chemotherapy vs. Pembrolizumab Plus Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma
3 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
This phase III trial compares chemotherapy versus an immune checkpoint inhibitor drug called pembrolizumab plus chemotherapy in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or that does not respond to treatment (refractory). The usual approach for patients with classical Hodgkin lymphoma is treatment with standard chemotherapy, including drugs that are Food and Drug Administration (FDA)-approved. If this treatment puts a patient into remission, high dose chemotherapy and stem cell transplant may be used to increase the likelihood of a cure. Hodgkin lymphoma is capable of inhibiting the immune system from killing it. Pembrolizumab is a checkpoint inhibitor that may be able to stop this inhibition, allowing the immune system to attack the lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Aug 2023
Longer than P75 for phase_3
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 2, 2023
CompletedFirst Posted
Study publicly available on registry
February 3, 2023
CompletedStudy Start
First participant enrolled
August 10, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2028
March 20, 2024
March 1, 2024
4.9 years
February 2, 2023
March 19, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Event free survival (EFS)
Events include: failure to achieve partial remission (PR) or complete remission (CR) to salvage chemotherapy, failure to achieve a CR post high dose chemotherapy and autologous stem cell transplant (HDT-ASCT), progression, receipt of unplanned radiation or brentuximab vedotin maintenance, or death. Patients who have not experienced any of these events will be censored at the date they are last known to be progression free. Kaplan-Meier method will be used to estimate EFS, including medians and confidence intervals. Comparison of EFS between treatment arms will be conducted based on intent-to-treat principle using a one-sided stratified log-rank test with the stratification factors.
Time from randomization to the earlier of events listed in description field, assessed up to 15 years
Lugano-based response
Will be assessed using positron emission tomography/computed tomography (PET/CT) scan with Deauville score. Will assess the diagnostic performance of baseline metabolic tumor volume (TMTV) in predicting response (CR+PR vs no response) at pre-transplant/post-salvage, overall and by study arm. Diagnostic performance of baseline TMTV will be assessed using area under the receiver operator characteristic curve (ROC AUC) analysis, where the reference standard is pre-transplant/post-salvage response (CR/PR).
Pre-transplant/post-salvage therapy
Secondary Outcomes (2)
Percentage change in TMTV (delta TMTV)
Baseline to pre-transplant/post-salvage therapy
Baseline TMTV and delta TMTV
Baseline and pre-transplant/post-salvage therapy
Study Arms (2)
Arm A (chemotherapy regimen, HDT-ASCT)
ACTIVE COMPARATORSALVAGE THERAPY: Patients receive 1 of 3 chemotherapy regimens as clinically indicated: 1) ifosfamide IV, carboplatin IV, and etoposide IV; 2) gemcitabine IV, vinorelbine IV, and pegylated liposomal doxorubicin IV; or 3) brentuximab vedotin IV and bendamustine IV. Patients then undergo a PET/CT scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment. HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant. MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated.
Arm B (chemotherapy regimens+pembrolizumab, HD-ASCT)
EXPERIMENTALSALVAGE THERAPY: Patients receive pembrolizumab IV plus 1 of 3 chemotherapy regimens specified in Arm A as clinically indicated. Patients then undergo a PET scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve SD or PD come off study treatment. HDT-ASCT: Patients undergo ASCT. Patients may also receive a standard preparative chemotherapy regimen as clinically indicated. Patients who achieve PR prior to ASCT may also undergo RT as clinically indicated. Patients who went into ASCT with PR also undergo a PET/CT scan 30 days post-transplant. MAINTENANCE THERAPY: Patients may receive brentuximab vedotin IV as clinically indicated.
Interventions
Undergo ASCT
Given IV
Given IV
Given IV
Undergo PET/CT and CT
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo PET/CT
Undergo RT
Receive standard preparative chemotherapy regimen
Given IV
Eligibility Criteria
You may qualify if:
- Patient must be \>= 5 years of age and =\< 75 years of age
- Patient must have relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after frontline (first line of chemotherapy) as evidenced by Fludeoxyglucose F-18 (FDG) avid on PET scan. If regimen is adjusted based on PET2 results or toxicity during frontline therapy, this will only be considered one line of therapy. Prior checkpoint inhibitor is completed \> 6 months prior to randomization
- Patients \>= 18 years of age must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. Pediatric patients (16-17 years of age) must have a Karnofsky performance level \>= 50%. Pediatric patients (5-15 years of age) must have a Lansky performance level \>= 50
- Patient must be deemed fit for high dose chemo and autologous stem cell transplant
- Patient must have the ability to understand and the willingness to sign a written informed consent document. Pediatric patients (\< 18 years of age) and patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible. Child assent must be obtained as appropriate in accordance with institutional guidelines
- Absolute neutrophil count (ANC) \>= 1000/mcL (must be obtained =\< 7 days prior to randomization)
- If disease includes marrow involvement or hypersplenism, please reference the below revised requirement:
- ANC \>= 500/mcL
- Platelets \>= 75,000/mcL (must be obtained =\< 7 days prior to randomization)
- If disease includes marrow involvement or hypersplenism, please reference the below revised requirement:
- Platelets \>= 25,000/mcL
- Total bilirubin =\< 2x institutional upper limit of normal (ULN) (must be obtained =\< 7 days prior to randomization)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN for age (must be obtained =\< 7 days prior to randomization)
- Glomerular filtration rate (GFR) \>= 50 mL/min/1.73m\^2 73m\^2 for patients \>= 18 years of age (must be obtained =\< 7 days prior to randomization)
- Pediatric patients (\< 18 years old) must have a creatinine clearance OR radioisotope GFR \>= 70 mL/min/1.73 m\^2 OR serum creatinine below the maximum based on age/gender as follows (derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention \[CDC\]):
- +12 more criteria
You may not qualify if:
- Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
- All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
- A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Additionally, patients of childbearing potential must continue contraception measures for 4 months after the last dose of pembrolizumab, 6 months after the last dose of vinorelbine and for 3 months after the last dose of bendamustine. Male patients must continue contraception measures for 6 months after the last dose of ifosfamide and for 3 months after the last dose of vinorelbine. Patients must also not breastfeed while on study treatment and for 4 months after the last dose of Pembrolizumab and 9 days after the last dose of vinorelbine
- Patient must not have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or have current pneumonitis/interstitial lung disease
- Patient must not have the following symptomatic autoimmune disorders: rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, Sjögren's syndrome, or autoimmune vasculitis (e.g., Wegener's Granulomatosis), or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone). Patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study.
- Replacement doses of steroids for patients with adrenal insufficiency are allowed.
- Additionally, patients must not have an autoimmune disease that is felt by the treating physician to have the potential to be exacerbated by checkpoint inhibition
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Vaishalee P Kenkre
ECOG-ACRIN Cancer Research Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 2, 2023
First Posted
February 3, 2023
Study Start
August 10, 2023
Primary Completion (Estimated)
June 30, 2028
Study Completion (Estimated)
June 30, 2028
Last Updated
March 20, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.