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

NCT03331341 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 9805NCI-2017-01718RG1001581
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Classical Hodgkin Lymphoma

Keywords

Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• PART A: Number of Participants Who Complete of 2 Cycles of Adriamycin, Pembrolizumab, Vinblastine and Dacarbazine (APVD)

  Number of participants who complete 2 cycles of treatment without a dose delay of \>3 weeks. Toxicity leading to dose delay will be assessed using CTCAE v5.0.

  At the end of Cycle 2 (each cycle is 28 days)

• PART B: Event Free Survival at 1 Year

  Number of participants who are event free at 1 year. An event is defined as progression, biopsy proven recurrence, initiation of next line of chemotherapy, or death.

  At the end of 1 year after completing 2 cycles of treatment (each cycle is 28 days)

Secondary Outcomes (1)

• Proportion of Fludeoxyglucose F-18 (FDG)-Positron Emission Tomography PET2 Negative (Deauville Score 1-3) Patients After 2 Cycles of APVD

  After 2 cycles (each cycle is 28 days)

Study Arms (1)

Treatment (APVD)

EXPERIMENTAL

PART A: 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. PART B: Patients receive doxorubicin hydrochloride IV, vinblastine IV, dacarbazine IV, and pembrolizumab IV as in part A, but undergo a total of 6 treatment cycles.

Drug: Dacarbazine; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Vinblastine

Interventions

Dacarbazine DRUG

Given IV

Also known as: 4-(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-139007

Treatment (APVD)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-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, Rubex

Treatment (APVD)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (APVD)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (APVD)

Vinblastine DRUG

Given IV

Also known as: Vincaleucoblastine, VLB

Treatment (APVD)

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 cHL that has not been previously treated
• Part A: Any stage
• Part B: Must be stage 3 or 4
• Patients must be appropriate candidates for at least 2 cycles of doxorubicin hydrochloride (adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) (6 cycles for Part B patients) or doxorubicin hydrochloride, vinblastine, dacarbazine (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 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 10 days of treatment
• 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)
• Hemoglobin \>= 8 g/dL. Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. There is no lower limit to cytopenias if related to bone marrow involvement
• Serum creatinine \< 1.5 mg/dl or creatinine clearance greater than 30/ml per minute by Cockcroft Gault formula
• Total bilirubin =\< 1.5 times upper limit of normal OR direct bilirubin =\< upper limit of normal (ULN) for participants with total bilirubin levels \> 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times upper limit of normal (=\< 5 x ULN for participants with liver metastases)

You may not qualify if:

• 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/interstitial lung disease that required corticosteroids
• Current use of supplemental oxygen
• Is known to have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial treatment. Administration of killed vaccines is allowed

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Lynch RC, Ujjani CS, Poh C, Warren EH, Smith SD, Shadman M, Till B, Raghunathan VM, Alig S, Alizadeh AA, Gulhane A, Chen DL, Tseng Y, Coye H, Shelby M, Ottemiller S, Keo S, Verni K, Du H, Vandermeer J, Gaston A, Rasmussen H, Martin P, Marzbani E, Voutsinas J, Gopal AK. Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. Blood. 2023 May 25;141(21):2576-2586. doi: 10.1182/blood.2022019254.

  PMID: 36913694 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Dacarbazine; Doxorubicin; pembrolizumab; Vinblastine

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)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Ryan Lynch, Associate Professor
• Organization: University of Washington

rclynch@uw.edu

206-606-1739

Study Officials

• Ryan Lynch

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 6, 2017
• Study Start: January 9, 2019
• Primary Completion: December 21, 2023
• Study Completion: December 21, 2023
• Last Updated: August 5, 2025
• Results First Posted: January 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)