Brentuximab Vedotin, Cyclosporine, and Verapamil Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

NCT03013933 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16414NCI-2016-02062
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of brentuximab vedotin and cyclosporine when given together with verapamil hydrochloride in treating patients with Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunosuppressive therapies, such as cyclosporine, may improve bone marrow function and increase blood cell counts. Verapamil hydrochloride may increase the effectiveness of brentuximab vedotin by overcoming drug resistance of the cancer cells. Giving brentuximab vedotin, cyclosporine, and verapamil hydrochloride may work better in treating patients with Hodgkin lymphoma.

Conditions

Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

  Up to 21 days

Secondary Outcomes (7)

• Overall response rate (complete response + partial response)

  Up to 2 years

• Complete response rate assessed by Cheson 2014 criteria

  Up to 2 years

• Duration of overall response

  Up to 2 years

• Duration of complete response

  Up to 2 years

• Overall survival

  From start of protocol treatment to time of death (due to any cause), assessed up to 2 years

Other Outcomes (2)

• Percentage of CD30, CD68, and drug exporters

  Up to 2 years

• Pharmacokinetics of monomethyl auristatin E (MMAE)

  Up to 2 years

Study Arms (1)

Treatment (cyclosporine, verapamil, brentuximab vedotin)

EXPERIMENTAL

Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Brentuximab Vedotin; Drug: Cyclosporine; Other: Pharmacokinetic Study; Drug: Verapamil; Drug: Verapamil Hydrochloride

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Treatment (cyclosporine, verapamil, brentuximab vedotin)

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya

Treatment (cyclosporine, verapamil, brentuximab vedotin)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (cyclosporine, verapamil, brentuximab vedotin)

Verapamil DRUG

Given PO

Treatment (cyclosporine, verapamil, brentuximab vedotin)

Verapamil Hydrochloride DRUG

Given PO

Also known as: (+-)-Verapamil hydrochloride, Calan, Isoptin SR, Verelan

Treatment (cyclosporine, verapamil, brentuximab vedotin)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent
• Voluntary written informed consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Weight over 40 kg
• Life expectancy of greater than 3 months
• Patients must have histologically documented or cytologically confirmed Hodgkin lymphoma
• Patient must have measurable disease \> 1.5 cm evidenced by computed tomography (CT) of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans
• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from archival tissue of a biopsy that was performed after the most recent systemic therapy. Exception can be granted by the principal investigator (PI) if a biopsy is not feasible and/or safe
• Patients must be either refractory to or relapsed after at least 1 line of therapy
• Prior brentuximab vedotin is allowed; expansion cohort is defined as:
• Expansion cohort: BV refractory: Patient who had prior exposure to BV, and either - achieved a best response of stable disease (SD) or progressive disease (PD) or - achieved a best response of complete response (CR)/PR but developed PD while on active BV treatment
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• Prior chemotherapy or radiation therapy is allowed if received \>= 3 weeks before study enrollment
• Prior hematopoietic transplantation is allowed (autologous and/or allogeneic)
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3; filgrastim can be given prior to enrollment to achieve target ANC \>= 1000/uL (to be performed within 10 business days prior to day 1)
• Platelets \>= 50,000/mm\^3; NOTE: platelet transfusion and packet red blood cell transfusion can be given prior to enrollment to achieve a target platelet (Plt) \>= 50,000/uL and hemoglobin of \>= 8.5 g/dL (to be performed within 10 business days prior to day 1)

You may not qualify if:

• Patients who are hematopoietic stem cell transplant candidates are excluded
• Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
• Patients may be on steroids prior to initiation of treatment, provided that, by cycle 1 day 1, steroid use is tapered down to less than or equal to 20 mg/day of prednisone
• Patients may not be receiving any other investigational agents, or concurrent biological therapy, chemotherapy, or radiation therapy
• Active graft versus host disease (GVHD) or on immunosuppressive medication of GVHD
• Recent infection requiring intravenous anti-infective treatment that was completed =\< 14 days before enrollment
• Unresolved toxicities from prior anticancer therapy, defined as having resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 4.03), grade 0 or 1, with the exception of alopecia
• Baseline grade II peripheral neuropathy
• Hypersensitivity to BV or history of allergic reaction attributed to compounds of similar chemical or biologic composition of BV
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
• Patients should not have any uncontrolled illness including ongoing or active infection
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
• Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
• Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) \>= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of \>= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; Cyclosporine; Cyclosporins; Pharmacogenomic Variants; Verapamil

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)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Polymorphism, Genetic; Genetic Variation; Genetic Phenomena; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Alex F Herrera

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 9, 2017
• Study Start: May 3, 2017
• Primary Completion: May 24, 2022
• Study Completion: May 24, 2022
• Last Updated: February 22, 2024

Record last verified: 2024-02

Locations

US (1)