A Phase 1 Trial of Brentuximab Vedotin Plus Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-Cell Lymphomas
A Phase 1 Trial of Brentuximab Vedotin Plus Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-Cell Lymphomas
This phase I trial studies the side effects and best dose of lenalidomide when given together with brentuximab vedotin in treating patients with T-cell lymphomas that have come back or do not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, 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. Giving brentuximab vedotin and lenalidomide may work better in treating patients with T-cell lymphomas.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD)/Recommended Phase 2 dose (RP2D) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory cutaneous T-cell lymphoma (CTCL).
II. Assess safety and tolerability of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL.
SECONDARY OBJECTIVES:
I. Estimate the rate of objective global response that lasts at least 4 months (ORR4) , complete response (CR) rate, progression-free survival (PFS) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL.
II. Estimate the rate and duration of clinically meaningful reduction in pruritus (CMRP).
III. Correlate response to baseline CD30 levels in tissue samples.
TERTIARY OBJECTIVES:
I. Estimate the response endpoints incorporating Lugano response criteria for patients with PET+ disease.
II. Explore temporal gene expression profile in skin/ blood samples that may predict response to combination therapy.
OUTLINE: This is a dose-escalation study of lenalidomide.
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 17 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 12 months.
Inclusion Criteria:
Documented informed consent of the participant and/or legally authorized representative
Registered into mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program
Women of childbearing potential: adhere to scheduled pregnancy testing as required in the Revlimid REMS program
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Histologically confirmed cutaneous T-cell non-Hodgkin lymphoma (CTCL) per World Health Organization (WHO) classification 2016 including, mycosis fungoides (MF) or Sezary syndrome (SS); phase 1 : >= stage IIB OR >= stage IB-IIA folliculotropic/transformed MF; expansion cohort: >= stage IB
Relapsed/refractory disease
Failed >= 2 prior systemic therapies
CD30-positivity by immunohistochemistry of >= 1%
Measurable disease per modified Severity Weighted Assessment and/or Sezary count
Fully recovered from acute toxicities (except alopecia) of all prior therapies to Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1
May have received either brentuximab vedotin or lenalidomide/immunomodulatory imide drugs (IMiD) without dose modification/delay due to toxicity
* IMiDs defined as thalidomide analogues
If received prior brentuximab vedotin or lenalidomide, must be able to tolerate the dose level to which the participant will be enrolled to
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Absolute neutrophil count (ANC) >= 1,000/mm^3
* NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Platelets >= 75,000/mm^3
* NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Total bilirubin =< 1.5 X upper limit of normal (ULN) OR if Gilbert's syndrome =< 3.0 X ULN
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Aspartate aminotransferase (AST) =< 2 x ULN
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Alanine aminotransferase (ALT) =< 2 x ULN
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Women of childbearing potential (WOCBP): 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
Agreement by WOCBP and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
Stem cell transplantation
Monoclonal antibody within 28 days prior to day 1 of protocol therapy
Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating day 1 of protocol therapy
Any skin-directed therapy within 14 days prior to day 1 of protocol therapy
Any radiation therapy within 21 days prior to day 1 of protocol therapy
Immunosuppressive medication within 14 days prior to day 1 of protocol therapy; the following are exceptions to this criterion:
Live, attenuated vaccine within 30 days prior to day 1 of protocol therapy
Disease free of prior malignancies for >= 5 years with the exception of:
Allergic reaction/hypersensitivity to lenalidomide or history of anaphylactic shock to brentuximab vedotin in the past
Female only: pregnant or breastfeeding
Acute infection requiring systemic treatment
Known history of human immunodeficiency virus (HIV) infection
Active hepatitis B or C infection
Central nervous system involvement by lymphoma, including leptomeningeal involvement
History of progressive multifocal leukoencephalopathy (PML)
Current peripheral neuropathy >= grade 2 or patients with the demyelinating form of Charcot-Marie-Tooth syndrome
Unstable cardiac disease as defined by one of the following:
History of vascular disease (e.g. deep vein thrombosis, stroke)
Major surgery (as defined by the investigator) within the 28 days prior to day 1 of protocol therapy
Incidence of gastrointestinal disease that may significantly alter the absorption of lenalidomide
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc.
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)