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

NCT03077828 | Unknown Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 16H07P30CA060553NCI-2016-01439STU00203658
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

Brief 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. 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.

Conditions

Lymphocyte-Rich Classical Hodgkin Lymphoma; Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma; Recurrent Mixed Cellularity Classical Hodgkin Lymphoma; Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma; Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma; Refractory Mixed Cellularity Classical Hodgkin Lymphoma; Refractory Nodular Sclerosis Classical Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (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).

  Up to 59 days

Secondary Outcomes (3)

• Incidence of Adverse Events

  Up to 2 years

• Event Free Survival (EFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)

EXPERIMENTAL

Patients 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.

Drug: Carboplatin; Drug: Etoposide; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)

Ifosfamide DRUG

Given IV

Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, etoposide, carboplatin, ifosfamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Northwestern University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (1)

• 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.

  PMID: 36928527 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Carboplatin; Etoposide; Ifosfamide; pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jane N. Winter, M.D.
• Organization: Northwestern University

j-winter@northwestern.edu

3126954538

Study Officials

• Jane N. Winter, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jane N. Winter, M.D.

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: March 13, 2017
• Study Start: April 21, 2017
• Primary Completion: December 30, 2020
• Study Completion: December 1, 2024
• Last Updated: June 2, 2023
• Results First Posted: June 2, 2023

Record last verified: 2023-05

Locations

US (6)