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Recurrent Hodgkin LymphomaPhase 1NCT03013933

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

A Phase 1 study testing Brentuximab Vedotin, Cyclosporine and Pharmacokinetic Study in people with Recurrent Hodgkin Lymphoma and Refractory Hodgkin Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Brentuximab Vedotin, Cyclosporine and Pharmacokinetic Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
3 May 2017to 24 May 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care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
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  • 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)
  • Hemoglobin >= 8.5 g/dL (to be performed within 10 business days prior to day 1)
  • Total bilirubin within 1.5 x the upper limit of normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible (to be performed within 10 business days prior to day 1)
  • Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) unless demonstrated Hodgkin lymphoma involvement of the liver (to be performed within 10 business days prior to day 1)
  • Alanine aminotransferase (ALT) =< 3 x ULN unless demonstrated Hodgkin lymphoma involvement of the liver (to be performed within 10 business days prior to day 1)
  • Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula and/or 24 hour (hr) urine analysis as needed (to be performed within 10 business days prior to day 1)
  • If not receiving anticoagulants: international normalization ratio (INR) OR prothrombin (PT) =< 1.5 x ULN; if on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 10 business days prior to day 1)
  • If not receiving anticoagulants: activated partial thromboplastin time (aPTT) =< 1.5 x ULN; if on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 10 business days prior to day 1)
  • Female of childbearing potential: negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 10 business days prior to day 1)
  • In patients who are to receive VRP, base systolic blood pressure (SBP) > 110; diastolic blood pressure (DBP) > 60 and baseline heart rate > 60 (to be performed within 10 business days prior to day 1)
  • Cardiac function (12 lead-electrocardiogram [ECG] versus [vs] non 12 led ECG) shows no underlying arrhythmia or heart blocks (for VRP only) (to be performed within 10 business days prior to day 1)
  • Female subjects must be either post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intra-uterine deice, diaphragm with spermicide, condom with spermicide, or abstinence) beginning prior to study entry, for the duration of the study, and for six months duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • Male subjects must agree to use an acceptable method of contraception beginning prior to study entry, for the duration of the study, and for six months following duration of study participation

Who cannot join

  • 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
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  • 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
  • Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
  • Known active human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; subjects who have an undetectable HIV viral load with CD4 >= 200 and are on highly active antiretroviral therapy (HAART) medication are allowed; subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded; patients who have had hepatitis C but have finished treatment and are PCR negative will be allowed; (testing to be done only in patients suspected of having infections or exposures)
  • Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
  • Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase I Trial of Brentuximab Vedotin Plus MDR1 Inhibitors in Relapsed/Refractory Hodgkin Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Evaluate the safety and tolerability of the combination of brentuximab vedotin (BV) plus MDR1 inhibitors cyclosporine (CsA)/verapamil hydrochloride (verapamil [VRP]).

SECONDARY OBJECTIVES:

  1. Obtain estimates of overall response rate (ORR), complete response (CR) rate, and response duration in patients treated with the combination of BV plus CsA/VRP.

II. Estimate overall and progression-free survival in patients treated with the combination of BV plus CsA/VRP.

III. Characterize pharmacokinetics of plasma monomethyl auristatin E (MMAE) in cycle 1 (for expansion cohort only).

OUTLINE: This is a dose-escalation study of brentuximab vedotin and cyclosporine.

Patients receive cyclosporine orally (PO) twice daily (BID) on days 1-5, verapamil hydrochloride PO four times daily (QID) on days 1-5, and brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients who have not progressed are followed up every 6 months until disease progression, start of a new lymphoma therapy, 2 years post treatment, or study completion, whichever is earlier. Patients who progress are followed up periodically.

Being tested
Brentuximab Vedotin, Cyclosporine, Pharmacokinetic Study, Verapamil, Verapamil Hydrochloride
Medical subject headings
Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brentuximab VedotinDrug

    Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35

    Given IV

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO

  • Pharmacokinetic StudyOther

    Also called PHARMACOKINETIC, PK Study

    Correlative studies

  • VerapamilDrug

    Given PO

  • Verapamil HydrochlorideDrug

    Also called (+-)-Verapamil hydrochloride, Calan, Isoptin SR, Verelan

    Given PO

Study groups in NCT03013933
Study groupRoleWhat they receive
Treatment (cyclosporine, verapamil, brentuximab vedotin)ExperimentalPatients 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.
Receives: Drug: Brentuximab Vedotin; Drug: Cyclosporine; Other: Pharmacokinetic Study; Drug: Verapamil; Drug: Verapamil Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity

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

    Measured: Up to 21 days

Secondary outcomes (7)

  1. Overall response rate (complete response + partial response)

    Will be assessed by Cheson 2014 criteria. Will be estimated with the 95% exact binomial confidence interval.

    Measured: Up to 2 years

  2. Complete response rate assessed by Cheson 2014 criteria

    Will be estimated with the 95% exact binomial confidence interval and using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

    Measured: Up to 2 years

  3. Duration of overall response

    Will be estimated using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

    Measured: Up to 2 years

  4. Duration of complete response

    Will be estimated using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

    Measured: Up to 2 years

  5. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

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

  6. Progression-free survival

    Will be estimated using the product-limit method of Kaplan and Meier along with Greenwood estimator of standard error.

    Measured: From start of treatment to time of disease progression or death due to any cause, whichever occurs first, assessed up to 2 years

  7. Incidence of adverse events assessed

    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Observes toxicities will be summarized by type, severity, date of onset, duration, reversibility, and attribution.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2017 (estimated)
  2. Study start3 May 2017
  3. Primary completion24 May 2022
  4. Study completion24 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03013933
Sponsor's protocol ID
16414
Other IDs
NCI-2016-02062, 16414
Status last verified
Feb 2024
First submitted
4 Jan 2017
Last updated
22 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Brentuximab Vedotin, Cyclosporine and Pharmacokinetic Study in people with Recurrent Hodgkin Lymphoma and Refractory Hodgkin Lymphoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (time frame: Up to 21 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03013933.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.

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