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Lymphocyte-Rich Classical Hodgkin LymphomaPhase 2NCT03077828

Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

A Phase 2 study testing Carboplatin, Etoposide and Ifosfamide in people with Lymphocyte-Rich Classical Hodgkin Lymphoma and Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma, run by Northwestern University at 6 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this research study is to evaluate a new drug Pembrolizumab in combination with chemotherapy, for Relapsed/Refractory Hodgkin Lymphoma. The chemotherapy regimen is called "ICE" and includes three drugs: ifosfamide, carboplatin, and etoposide. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Etoposide and Ifosfamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
6 sitesUnited States
Study dates
21 Apr 2017to Dec 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed diagnosis of classical Hodgkin lymphoma including nodular sclerosis, mixed cellularity, lymphocytic-rich, and lymphocyte depleted subtypes by the 4th edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008
  • Patients must have disease with FDG-PET/CT avidity
  • Patients must have relapsed/refractory disease, with at least one line of prior chemotherapy, but =< 2 prior lines of treatment, for Hodgkin lymphoma; NOTE: Patients must not have had prior immune checkpoint inhibitors; however, there are no other limitations to prior agent or regimen types
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Patients must have adequate organ and bone marrow function within 10 days of registration, as defined below:
  • Absolute neutrophil count >= 1,000/mcL (in the absence of granulocyte colony stimulating factor (GCSF) for >= 14 days)
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  • Platelets >= 75,000/mcl (in the absence of platelet transfusion for >= 14 days)
  • Hemoglobin >= 7g/dL (transfusion permitted)
  • Total bilirubin =< 2 x institutional upper limit of normal (ULN); if total bilirubin is > 2 x ULN, the direct bilirubin must be normal
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 2.5 x institutional ULN
  • Creatinine =< 2 x ULN or creatinine clearance (CrCl) > 30 ml/min
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registration; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Females of childbearing potential (FOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months) NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Who cannot join

  • Patients who have had chemotherapy, radiotherapy, monoclonal antibody (mAb), or targeted small molecule therapy within 4 weeks of study registration are not eligible; those who have not recovered from adverse events (grade 1 or baseline) due to such agents administered more than 4 weeks earlier are not eligible
  • Patients may not be currently receiving any other investigational agents within 4 weeks of study registration
  • Patients must not have had prior exposure to any immune checkpoint inhibitors including anti-PD-1, anti-PD-L1 agents, anti-PD-L2 agents, or anti-CTLA-4 monoclonal antibodies
  • Patients must not have known central nervous system (CNS) involvement
  • Patients must not have had prior stem cell transplantation (autologous or allogeneic)
  • Patients must not have persistent diarrhea greater than National Cancer Institute (NCI) CTCAE grade 2 at the time of study registration, despite medical management
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  • Patients must not have a history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, noninfectious pneumonitis
  • Patients with known immunodeficiency, known autoimmune disease, or concurrent use of immunomodulatory agents including systemic steroids within 7 days prior to registration, are ineligible
  • Patients must not have co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens; this includes, 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
  • Patients must not have a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Patients with known human immunodeficiency virus (HIV) infection or active TB (Bacillus tuberculosis) are not eligible
  • Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are not eligible
  • Patients must not have a hypersensitivity to pembrolizumab or any of its excipients
  • Patients must not have received a live vaccine within 30 days of registration Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed)
  • Patients must not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Patients who are unwilling or unable to comply with the protocol or have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial are not eligible

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Northwestern University

    Chicago, Illinois, 60611

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • University of Rochester

    Rochester, New York, 14642

Other trials in United States

About this study

Official title: Phase II Trial of Pembrolizumab in Combination With ICE Salvage Chemotherapy for Relapsed/Refractory Hodgkin Lymphoma

The purpose of this research study is to evaluate a new drug Pembrolizumab in combination with chemotherapy, for Relapsed/Refractory Hodgkin Lymphoma. The chemotherapy regimen is called "ICE" and includes three drugs: ifosfamide, carboplatin, and etoposide. Pembrolizumab is currently Food and Drug Administration (FDA) approved for the treatment of some patients with melanoma, lung cancer and head and neck cancer, but has not yet been approved for the treatment of Relapsed/Refractory Hodgkin Lymphoma. The 'ICE' regimen of chemotherapy is currently FDA approved for the treatment of Relapsed/Refractory Hodgkin Lymphoma, but has not yet been investigated in combination with pembrolizumab for this disease. For patients who have a relapse of their Hodgkin's lymphoma, retreatment with chemotherapy followed by a stem cell transplant is recommended. We know that obtaining a complete remission (not able to detect any disease on scans) is very important prior to proceeding to the stem cell transplant. Patients with negative scans have a lower chance of the disease coming back and a higher chance of achieving a long-term cure.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the complete response rate by fludeoxyglucose- positron emission tomography/computed tomography (FDG-PET/CT) prior to autologous hematopoietic stem cell transplant (AHSCT) with the combination of pembrolizumab and ifosfamide, carboplatin, etoposide (ICE) salvage chemotherapy for relapsed/refractory Hodgkin lymphoma.

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability of pembrolizumab in combination with salvage high-dose chemotherapy according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03.

II. To estimate the event free survival (EFS) at 2 years from start of treatment.

III. To estimate the overall survival (OS) at 2 years from start of treatment.

TERTIARY OBJECTIVES:

  1. To characterize PD-1 pathway specific expression and correlate with response.

II. To characterize serum biomarkers of immune and inflammatory response during treatment.

III. To characterize levels of soluble PD-L1 related to treatment with pembrolizumab.

IV. To characterize T-lymphocyte subset changes to treatment with pembrolizumab.

  1. To investigate the prevalence and clinical correlation of chromosome 9p24.1 mutations for this population.

VI. To evaluate the effect on stem cell harvest following treatment with pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, etoposide IV over 60 minutes on days 1-3 of courses 1-2, carboplatin IV over 60 minutes on day 2 of courses 1-2, and ifosfamide IV over 24 hours on day 2 of courses 1-2. Pembrolizumab in combination with ICE chemotherapy repeats every 21 days for 2 courses, patients will then receive pembrolizumab as monotherapy on course 3.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years.

Being tested
Carboplatin, Etoposide, Ifosfamide, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Hodgkin Disease

What participants receive

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

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • EtoposideDrug

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

    Given IV

  • IfosfamideDrug

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

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03077828
Study groupRoleWhat they receive
Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1, etoposide IV over 60 minutes on days 1-3 of courses 1-2, carboplatin IV over 60 minutes on day 2 of courses 1-2, and ifosfamide IV over 24 hours on day 2 of courses 1-2. Pembrolizumab in combination with ICE chemotherapy repeats every 21 days for 2 courses, patients will then receive pembrolizumab as monotherapy on course 3.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. Complete Response Rate

    To determine the complete response rate by FDG-PET/CT prior to AHSCT with the combination of pembrolizumab and ICE salvage chemotherapy for relapsed/refractory Hodgkin lymphoma. Response was assessed using Lugano criteria 2014.

    To address the primary aim, the proportion of patients with complete responses was calculated(defined as FDG-PET/CT Deauville score ≤ 3) as (number of responders) / (number of evaluable patients).

    Measured: Up to 59 days

Secondary outcomes (3)

  1. Incidence of Adverse Events

    Evaluate the safety and tolerability of pembrolizumab in combination with ICE salvage high-dose chemotherapy by measuring the frequency and severity of adverse events by type, severity (grade), timing, and attribution to pembrolizumab which will be assessed according the NCI-CTCAE version 4.03.

    Measured: Up to 2 years

  2. Event Free Survival (EFS)

    EFS will be defined as the length of time from treatment on protocol until the first occurrence of disease relapse, progression, re-initiation of cytotoxic chemotherapy, or death due to disease, or until last contact if the patient did not experience any of these, assessed up to 2 years.

    Measured: Up to 2 years

  3. Overall Survival (OS)

    OS will be defined as time from study enrollment until death, or until last contact if the patient did not die, assessed up to 2 years.

    Measured: Up to 2 years

Timeline

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

  1. First posted13 Mar 2017
  2. Study start21 Apr 2017
  3. Primary completion30 Dec 2020
  4. Study completionDec 2024 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03077828
Sponsor's protocol ID
NU 16H07
Other IDs
NU 16H07, P30CA060553, NCI-2016-01439, STU00203658
Status last verified
May 2023
First submitted
8 Mar 2017
Last updated
2 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bryan LJ, Casulo C, Allen PB, Smith SE, Savas H, Dillehay GL, Karmali R, Pro B, Kane KL, Bazzi LA, Chmiel JS, Palmer BA, Mehta J, Gordon LI, Winter JN. Pembrolizumab Added to Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Relapsed or Refractory Classic Hodgkin Lymphoma: A Multi-institutional Phase 2 Investigator-Initiated Nonrandomized Clinical Trial. JAMA Oncol. 2023 May 1;9(5):683-691. doi: 10.1001/jamaoncol.2022.7975.

    PubMed 36928527

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Etoposide and Ifosfamide in people with Lymphocyte-Rich Classical Hodgkin Lymphoma and Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma, run by Northwestern University at 6 sites in United States.

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 17 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Complete Response Rate (time frame: Up to 59 days). 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 NCT03077828, which also lists 1 linked publication.

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 2 Jun 2023; AzTrials last refreshed its copy on 8 Nov 2026.

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