Clinical Trials /

Doxorubicin Hydrochloride, Pembrolizumab, Vinblastine, and Dacarbazine in Treating Patients With Classical Hodgkin Lymphoma

NCT03331341

Description:

This phase II trial studies the side effects of doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine in treating patients with classical Hodgkin lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with pembrolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine may work better in treating classical Hodgkin lymphoma.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Doxorubicin Hydrochloride, Pembrolizumab, Vinblastine, and Dacarbazine in Treating Patients With Classical Hodgkin Lymphoma
  • Official Title: A Pilot Trial of Adriamycin, Pembrolizumab, Vinblastine, and Dacarbazine (APVD) for Patients With Untreated Classical Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 9805
  • SECONDARY ID: NCI-2017-01718
  • SECONDARY ID: 9805
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03331341

Conditions

  • Classical Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Dacarbazine4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007Treatment (APVD)
Doxorubicin Hydrochloride5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexTreatment (APVD)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (APVD)
VinblastineVincaleucoblastine, VLBTreatment (APVD)
DoxorubicinAdriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin, (8S-cis)-10-[(3-Amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7, 14-Hydroxydaunomycin, 23214-92-8Treatment (APVD)

Purpose

This phase II trial studies the side effects of doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine in treating patients with classical Hodgkin Lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with pembrolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine may work better in treating classical Hodgkin lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the safety of delivering 2 cycles doxorubicin hydrochloride (adriamycin),
      pembrolizumab, vinblastine and dacarbazine (APVD) to patients with previously untreated
      classical Hodgkin lymphoma (cHL).

      SECONDARY OBJECTIVES:

      I. To estimate the fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)2 negative
      (Deauville score 1-3) rate after 2 cycles of APVD.

      OUTLINE:

      Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine IV, and
      dacarbazine IV on days 1 and 15. Patients also receive pembrolizumab IV over 30 minutes on
      days 1 and 22 of cycle 1 and on day 15 of cycle 2. Treatment repeats every 28 days for up to
      2 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then for up to 5
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (APVD)ExperimentalPatients receive doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Patients also receive pembrolizumab IV over 30 minutes on days 1 and 22 of cycle 1 and on day 15 of cycle 2. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
  • Dacarbazine
  • Doxorubicin Hydrochloride
  • Pembrolizumab
  • Vinblastine
  • Doxorubicin

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have cHL that has not been previously treated (patients who have
             received one dose [day 1 cycle 1] of standard doxorubicin hydrochloride [adriamycin],
             bleomycin, vinblastine and dacarbazine [ABVD] or doxorubicin hydrochloride,
             vinblastine, dacarbazine [AVD] may be enrolled as long as they completed all the
             required standard of care baseline studies before enrollment and initiate study
             therapy by day 15 cycle 1)

          -  Patients must be appropriate candidates for at least 2 cycles of ABVD or AVD (this
             could include patients ranging from favorable risk early stage disease to poor
             prognosis advanced stage disease)

          -  Patients must have measurable FDG-avid disease defined by standard criteria (Lugano
             2014) and a minimum of 1.0 cm in diameter

          -  Patients must have a FDG-PET-computed tomography (CT) of chest, abdomen, and pelvis
             within 28 days of enrollment

          -  Patients should not have evidence of active central nervous system lymphoma

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0, 1, or 2

          -  Patients must have a left ventricular ejection (LVEF) >= 50% within 56 days of
             enrollment

          -  Patients must have adequate labs within 7 days of treatment unless cytopenia is
             thought to be due to underlying disease

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3 (without transfusion or growth factor
             support)

          -  Platelets >= 100,000/mm^3 (without transfusion or growth factor support)

          -  Serum creatinine < 1.5 mg/dl or creatinine clearance greater than 60/ ml per minute by
             the following formula (all tests must be performed within 28 days prior to
             registration)

          -  Total bilirubin < 1.5 times upper limit of normal

          -  Aspartate aminotransferase (AST) < 2.5 times upper limit of normal

          -  All patients must be informed of the investigational nature of this study and have
             given written consent in accordance with institutional and federal guidelines

          -  Patients must be anticipated to complete at least 2 cycles of chemotherapy

          -  Male subjects should agree to use an adequate method of barrier contraception starting
             with the first dose of study therapy through 120 days after the last dose of study
             therapy

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential 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; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year

        Exclusion Criteria:

          -  Patients known positive for human immunodeficiency virus (HIV), or infectious
             hepatitis type B or C

          -  Pregnant or nursing women; men or women of reproductive potential may not participate
             unless they have agreed to use an effective contraceptive method

          -  Patients with other prior malignancies except for adequately treated basal cell
             carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or
             other cancer from which the patient has been disease-free for 5 years or greater,
             unless approved by the protocol chair or co-chair

          -  Patients who have other medical conditions that would contraindicate treatment with
             aggressive chemotherapy (including active infection, uncontrolled hypertension,
             congestive heart failure, unstable angina pectoris, or myocardial infarction within
             the past 6 months, uncontrolled arrhythmia, severe pulmonary disease or requirement of
             supplemental oxygen)

          -  Active ischemic heart disease or congestive heart failure

          -  Concurrent use of other anti-cancer agents or experimental treatments

          -  Known current or prior autoimmune disease with the exception of vitiligo

          -  Active or prior history of pneumonitis that required corticosteroids

          -  Current use of supplemental oxygen

          -  Is known to have received a live vaccine within 30 days prior to the first dose of
             trial treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days after start of treatment
Safety Issue:
Description:Assessed using Common Terminology Criteria for Adverse Events version 4.0

Secondary Outcome Measures

Measure:Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)2 negative (Deauville score 1-3) rate
Time Frame:Up to 56 days (2 cycles)
Safety Issue:
Description:Proportion of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) 2 negative (Deauville score 1-3) patients after 2 cycles of doxorubicin hydrochloride (adriamycin), pembrolizumab, vinblastine and dacarbazine (APVD)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

September 5, 2019