Everolimus and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

NCT02254239 | Terminated Phase 1 DMC

• 3 other identifiers: MC1387NCI-2014-01804P30CA015083
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of everolimus when given together with brentuximab vedotin in treating patients with Hodgkin lymphoma that has come back (relapsed) or is not responding to treatment (refractory). Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Brentuximab vedotin may interfere with the ability of cancer cells to grow and spread by binding to a protein on the surface of cancer cells and then releasing a cancer-killing substance to them. Giving everolimus together with brentuximab vedotin may be a better treatment for Hodgkin lymphoma.

Conditions

Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of everolimus in combination with brentuximab vedotin, graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  21 days

Secondary Outcomes (7)

• Complete response (CR) rate

  Up to 1 year

• Duration of response

  From date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 1 year

• Overall response rate (ORR) (complete response [CR] or partial response [PR])

  Up to 1 year

• Progression-free survival

  Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 1 year

• Response evaluated according to positron emission tomography/computed tomography-based response criteria

  Up to 1 year

Other Outcomes (2)

• Change in cytokines

  Baseline to up to day 1 of course 2

• Change in serum immunoglobulin free light chain

  Baseline to up to day 1 of course 2

Study Arms (1)

Treatment (everolimus, brentuximab vedotin)

EXPERIMENTAL

Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or QOD on days 1-21. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity. Patients then receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or every other day on days 1-84 for 1 course. MAINTENANCE THERAPY: Beginning on course 17, patients receive everolimus PO QD, QOD, twice weekly, or thrice weekly on days 1-84. Courses repeat every 84 days in the absence of disease progression and unacceptable toxicity.

Drug: Brentuximab Vedotin; Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

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 (everolimus, brentuximab vedotin)

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Treatment (everolimus, brentuximab vedotin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (everolimus, brentuximab vedotin)

Pharmacological Study OTHER

Correlative studies

Treatment (everolimus, brentuximab vedotin)

Eligibility Criteria

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

You may qualify if:

• Biopsy-proven relapsed (response to last treatment \> 6 months duration), refractory (no response to last treatment or response duration \< 6 months) or residual Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy \< 180 days prior to registration on this protocol with no intervening therapy and tissue is available for translational research studies
• Eligible to receive standard brentuximab vedotin for relapsed Hodgkin lymphoma
• Measurable disease by CT or magnetic resonance imaging (MRI) or the CT portion of the PET/CT: must have at least one lesion that has a single diameter of \>= 2 cm
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Absolute neutrophil count (ANC) \>= 1000/uL
• Hemoglobin (Hgb) \>= 9 g/dl
• Platelet (PLT) \>= 75,000/uL
• Serum total bilirubin within normal range (or =\< 1.5 x upper limit of normal \[ULN\] if liver metastases are present; or total bilirubin =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
• Aspartate aminotransferase (AST) =\< 1.5 x ULN
• Alkaline phosphatase =\< 1.5 x ULN
• Serum creatinine =\< 1.5 x ULN
• Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Willing to return to Mayo Clinic for follow-up
• Willing to provide blood and tissue samples for correlative research purposes

You may not qualify if:

• Any of the following
• Pregnant women
• Nursing women
• Women of childbearing potential who are unwilling to employ highly effective contraception while on study treatment and for 6 months after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant
• Men of childbearing potential who are unwilling to employ highly effective contraception while on study treatment and for 6 months after the final dose of treatment and should not father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring
• Candidate for known standard therapy for the patient's disease that is potentially curative
• Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =\< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy
• Received wide field radiotherapy =\< 28 days or limited field radiation for palliation =\< 14 days prior to registration or who have not recovered from side effects of such therapy
• Receiving corticosteroids \> 20 mg of prednisone per day (or equivalent); Note: the dose should be noted on the medication record each cycle
• Persistent toxicities \>= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York Heart Association class III or IV
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months prior to registration, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• Severely impaired lung function as defined as spirometry and diffusion capacity of carbon monoxide (DLCO) that is less than 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air
• Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN (Note: optimal glycemic control should be achieved before starting everolimus)

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; Everolimus

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; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Patrick Johnston

  Mayo Clinic

  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: September 29, 2014
• First Posted: October 1, 2014
• Study Start: February 4, 2016
• Primary Completion: December 12, 2018
• Study Completion: December 12, 2018
• Last Updated: December 12, 2019

Record last verified: 2018-12

Locations

US (1)