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Recurrent Classic Hodgkin LymphomaPhase 3NCT05711628

A Trial Comparing Chemotherapy Versus Novel Immune Checkpoint Inhibitor (Pembrolizumab) Plus Chemotherapy in Treating Relapsed/Refractory Classical Hodgkin Lymphoma

A Phase 3 study testing Autologous Hematopoietic Stem Cell Transplantation, Bendamustine and Brentuximab Vedotin in people with Recurrent Classic Hodgkin Lymphoma and Refractory Classic Hodgkin Lymphoma, run by National Cancer Institute (NCI).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 5 to 75 years
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Bendamustine and Brentuximab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
10 Aug 2023to 30 Jun 2028
Phase
Phase 3
Are there results?
None posted in the registry

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 5 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
Show all 27Show fewer
  • 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]):
  • Age: 5 to < 6 years; Maximum Serum Creatinine (mg/dL): Male (0.8); Female (0.8)
  • Age: 6 to 10 years; Maximum Serum Creatinine (mg/dL): Male (1.0); Female (1.0)
  • Age: 10 to 13 years; Maximum Serum Creatinine (mg/dL): Male (1.2); Female (1.2)
  • Age: 13 to < 16 years; Maximum Serum Creatinine (mg/dL): Male (1.5); Female (1.4)
  • Age: >= 16 years; Maximum Serum Creatinine (mg/dL): Male (1.7); Female (1.4)
  • Patient must have a left ventricular ejection fraction (LVEF) >= 50%, as measured by echocardiogram, multi-gated acquisition (MUGA) scan, or functional cardiac imaging scan (or a shortening fraction of >= 27% for patients < 18 years of age only)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients >= 18 years of age 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

Who cannot join

  • 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

About this study

Official title: Randomized Phase III Trial of Chemotherapy vs. Pembrolizumab Plus Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the 2-year event free survival (EFS) of patients treated with pembrolizumab added to chemotherapy versus chemotherapy alone, in patients with relapsed/refractory (R/R) classical Hodgkin's lymphoma (cHL) who are intended to receive salvage therapy followed by high dose chemotherapy and autologous stem cell transplant (HDT-ASCT).

PRIMARY IMAGING OBJECTIVE:

  1. To assess the diagnostic performance of baseline total metabolic tumor volume (TMTV) in predicting response (complete remission [CR] + partial remission [PR] versus [vs] no response) at pre-transplant/post-salvage for each arm separately and overall.

SECONDARY OBJECTIVES:

  1. To assess the 2-year progression free survival (PFS) and overall survival (OS) in the transplanted population.

II. To assess the complete remission (CR) rate to salvage therapy. III. To assess the CR rate post HDT-ASCT. IV. To assess the post HDT-ASCT partial remission (PR) to CR conversion rate.

SECONDARY IMAGING OBJECTIVES:

  1. To assess the % change in TMTV (delta TMTV) from baseline to pre-transplant/post-salvage in predicting response (CR+PR vs no response) at pre-transplant/post-salvage for each arm separately and overall.

II. To assess baseline TMTV and delta TMTV in predicting EFS/OS for each arm separately and overall.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

SALVAGE THERAPY: Patients receive 1 of 3 chemotherapy regimens as clinically indicated: 1) ifosfamide intravenously (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 positron emission tomography (PET)/computed tomography (CT) scan. Patients who achieve a CR or PR proceed to HDT-ASCT. Patients who achieve stable disease (SD) or progressive disease (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 radiation therapy (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:

SALVAGE 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.

All patients undergo CT scans during follow-up.

Being tested
Autologous Hematopoietic Stem Cell Transplantation, Bendamustine, Brentuximab Vedotin, Carboplatin, Computed Tomography

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant

    Undergo ASCT

  • BendamustineDrug

    Also called SDX-105

    Given IV

  • Brentuximab VedotinDrug

    Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET/CT and CT

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • Pegylated Liposomal Doxorubicin HydrochlorideDrug

    Also called ATI-0918, Caelyx, Dox-SL, Doxil

    Given IV

  • PembrolizumabBiological

    Also called BCD-201, Keytruda, Lambrolizumab, MK-3475

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo RT

  • Transplant ConditioningOther

    Also called conditioning regimen

    Receive standard preparative chemotherapy regimen

  • VinorelbineDrug

    Also called Dihydroxydeoxynorvinkaleukoblastine

    Given IV

Study groups in NCT05711628
Study groupRoleWhat they receive
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.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Bendamustine; Drug: Brentuximab Vedotin; Drug: Carboplatin; Procedure: Computed Tomography; Drug: Etoposide; Drug: Gemcitabine; Drug: Ifosfamide; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: Transplant Conditioning; Drug: Vinorelbine
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.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Bendamustine; Drug: Brentuximab Vedotin; Drug: Carboplatin; Procedure: Computed Tomography; Drug: Etoposide; Drug: Gemcitabine; Drug: Ifosfamide; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: Transplant Conditioning; Drug: Vinorelbine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Time from randomization to the earlier of events listed in description field, assessed up to 15 years

  2. 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).

    Measured: Pre-transplant/post-salvage therapy

Secondary outcomes (2)

  1. Percentage change in TMTV (delta TMTV)

    Similar methods will be used as the primary imaging aim to assess the diagnostic performance of delta TMTV in predicting pre-transplant/post-salvage response (CR+PR vs no response). Delta TMTV will be defined as the percent change from baseline to pre-transplant/post-salvage [(post-salvage/pre-transplant - baseline)/baseline X 100].

    Measured: Baseline to pre-transplant/post-salvage therapy

  2. Baseline TMTV and delta TMTV

    Will assess baseline TMTV and delta TMTV in predicting EFS/overall survival (OS) for each arm separately and overall. The association between TMTV and EFS will be analyzed through a Cox regression model. TMTV will be analyzed individually as its absolute value and the percent change from baseline. We will also test if there is a difference by arm by including an interaction term in the model between TMTV and arm. The Kaplan-Meier method will be used to estimate EFS, including median survival times and confidence intervals. In addition to examining the TMTV, we will also analyze standard uptake value maximum (SUVmax) and total lesion glycolysis (TLG) with the same methods. The OS outcome will be analyzed in a similar manner.

    Measured: Baseline and pre-transplant/post-salvage therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2023
  2. Study start10 Aug 2023 (estimated)
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Why it stopped: Other - Protocol moved to Withdrawn

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05711628
Sponsor's protocol ID
NCI-2023-00575
Other IDs
NCI-2023-00575, EA4211, EA4211, U10CA180820
Status last verified
Mar 2024
First submitted
2 Feb 2023
Last updated
20 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Autologous Hematopoietic Stem Cell Transplantation, Bendamustine and Brentuximab Vedotin in people with Recurrent Classic Hodgkin Lymphoma and Refractory Classic Hodgkin Lymphoma, run by National Cancer Institute (NCI).

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 27 inclusion and 8 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: withdrawn, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Event free survival (EFS) (time frame: Time from randomization to the earlier of events listed in description field, assessed up to 15 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05711628.

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 20 Mar 2024.

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