Durvalumab With or Without Lenalidomide in Treating Patients With Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma

NCT03011814 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 16221NCI-2016-02061R01CA229510
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

Brief Summary

This randomized phase I/II trial studies the best dose and side effects of durvalumab and to see how well it works with or without lenalidomide in treating patients with cutaneous or peripheral T cell lymphoma that has come back and does not respond to treatment. Monoclonal antibodies, such as durvalumab, 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 durvalumab and lenalidomide may work better in treating patients with cutaneous or peripheral T cell lymphoma.

Conditions

Folliculotropic Mycosis Fungoides; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Sezary Syndrome; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (10)

• CTCL specific response assessed by Lugano Classification

  CTCL response was used to establish global response, which incorporates nodal, visceral and cutaneous lesions/disease. mSWAT tool was used for documenting responses in skin of patients with CTCL. PTCL specific response assessment criteria per Lugano Classification was used.

  Up to 12 months

• Dose limiting toxicity assessed by CTCAE version 4.03

  Observed toxicities was summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 84 days

• Duration of Complete Response

  Duration of complete response (CR) was defined as the time interval from the date of first documented complete response to the date of first documented disease relapse, progression or death whichever occurs first.

  Date when criteria for CR first met until time of loss of CR (relapse/recurrence) or death (as a result of MF/SS or acute toxicity of treatment), assessed up to 12 months

• Event-Free Survival

  Event-free survival was defined as the time interval from date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first. Event-free survival was estimated using the product-limit method of Kaplan and Meier.

  From date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, assessed up to 12 months

• Incidence of adverse events assessed by National Cancer Institute CTCAE version 4.03

  Observed toxicities was summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 90 days post-treatment

• Overall Response Rate (ORR)

  ORR was defined as proportion of patients with complete response (CR) and partial response (PR). The overall response rate and 95% Clopper Pearson binomial confidence interval (CI) was calculated.

  Up to 12 months

• Overall survival (OS)

  OS was defined as the time interval from date of first dose of study drug to date of death from any cause. OS was estimated using the product-limit method of Kaplan and Meier.

  From date of first dose of study drug to date of death from any cause, assessed up to 12 months

• Progression Free Survival (PFS)

  PFS was date of initiation of treatment to first date meets criteria for PD or death as a result of any cause.

  Date of initiation of treatment to first date meets criteria for progressive disease or death as a result of any cause, assessed up to 12 months

• Response duration

  95% Clopper Pearson binomial confidence interval will be calculated. Response rates will also be explored based on number/type of prior therapies.

  From the date of first documented response to the date of first documented disease relapse, progression or death whichever occurs first, assessed up to 12 months

• Time to response

  Date of initiation of treatment to date when criteria for response (PR or CR) first met, assessed up to 12 months

Secondary Outcomes (1)

• Clinically Meaningful Reduction in Pruritus (CMRP)

  Baseline up to 12 months

Study Arms (2)

Arm I (durvalumab)

EXPERIMENTAL

Patients receive durvalumab IV over 1 hour on day 1. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Other: Laboratory Biomarker Analysis

Arm II (durvalumab, lenalidomide)

EXPERIMENTAL

Patients receive durvalumab IV over 1 hour on day 1 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Arm I (durvalumab); Arm II (durvalumab, lenalidomide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (durvalumab); Arm II (durvalumab, lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Arm II (durvalumab, lenalidomide)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Registered into Revlimid REMS program
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Fully recovered from acute toxicities (except alopecia) of all prior therapies to Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1
• Relapsed/refractory disease
• Failed \>= 2 prior systemic therapies \*NOTE: For systemic ALCL prior systemic therapy must also include progression on brentuximab vedotin
• CUTANEOUS T-CELL LYMPHOMA (CTCL) ONLY
• Histologically confirmed mycosis fungoides (MF) or Sezary syndrome (SS); Phase 1: \>= stage IIB OR \>= stage IB-IIA folliculotropic/transformed MF; Phase 2: \>= stage IB
• Stage of disease according to TNMB classification
• Pathology report must be diagnostic or be consistent with MF/SS criteria
• SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathological features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria
• For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that has been recommended by the International Society of Cutaneous Lymphomas (ISCL) should be used
• Measurable disease per modified severity weighted assessment tool (mSWAT) and/or Sezary count
• Baseline skin biopsy taken within 6 months available for central review submission
• PERIPHERAL T-CELL LYMPHOMA (PTCL) ONLY

You may not qualify if:

• Immunotherapy with immune checkpoint inhibitors, cell-based therapies, or cancer vaccines
• Lenalidomide, thalidomide or other immunomodulatory drugs (IMiDs)
• Monoclonal antibody within 5 half-lives of the antibody prior to initiating protocol therapy
• Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating protocol therapy
• Any skin-directed therapy within 14 days prior to initiating protocol therapy
• Any radiation therapy within 21 days prior to initiating protocol therapy
• Immunosuppressive medication within 14 days prior to the first dose of study treatment; the following are exceptions to this criterion:
• Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) and are on stable dose for at least 28 days
• Systemic corticosteroids at physiologic doses of \< 10 mg/day of prednisone or equivalent
• Live, attenuated vaccine within 30 days prior to the first dose of protocol therapy
• History of pneumonitis (non-infectious) that required steroids or current pneumonitis
• Disease free of prior malignancies for \>= 5 years with the exception of:
• Currently treated squamous cell and basal cell carcinoma of the skin
• Carcinoma in situ of the cervix, or
• Surgically removed melanoma in situ of the skin (stage 0) with histological confirmed free margins of excision or

Sponsors & Collaborators

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

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Querfeld C, Palmer J, Han Z, Wu X, Yuan YC, Chen MH, Su C, Tsai NC, Smith DL, Hammond SN, Crisan L, Song JY, Pillai R, Rosen ST, Zain J. Phase 1 trial of durvalumab (anti-PD-L1) combined with lenalidomide in relapsed/refractory cutaneous T-cell lymphoma. Blood Adv. 2025 May 13;9(9):2247-2260. doi: 10.1182/bloodadvances.2024014655.

  PMID: 39951620 DERIVED

• Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.

  PMID: 32632956 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Lymphoma, T-Cell; Sezary Syndrome

Interventions

durvalumab; Immunoglobulin G; Disulfides; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Christiane Querfeld, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 5, 2017
• Study Start: March 8, 2017
• Primary Completion (Estimated): June 23, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

US (4)