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

Status: Approved

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. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Giving doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine may work better in treating classical Hodgkin lymphoma.

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 or 1
  • 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

Locations & Contacts

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Approved
Contact: Ajay Kumar Gopal
Phone: 206-606-2037

Trial Objectives and Outline

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.

EXPLORATORY OBJECTIVES:

I. Overall and progression free survival, association of biomarkers with early complete response (CR).

II. Predictive capacity of PET2 after APVD.

III. To evaluate the impact of APVD on T-cell repertoire and diversity.

IV. To evaluate the ability of this regimen to eradicate minimal residual disease as measured by next generation sequencing (NGS).

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 course 1 and on day 15 of cycle 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

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

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Fred Hutch / University of Washington Cancer Consortium

Principal Investigator
Ajay Kumar Gopal

Trial IDs

Primary ID 9805
Secondary IDs NCI-2017-01718
Clinicaltrials.gov ID NCT03331341