Brentuximab Vedotin and Lenalidomide for Relapsed or Refractory Diffuse Large B-cell Lymphoma

NCT02086604 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201404056
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase I clinical trial studies the side effects and maximum tolerated dose (MTD) of the combination of brentuximab vedotin (BV) and lenalidomide in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Conditions

Lymphoma, Large B-Cell, Diffuse

Outcome Measures

Primary Outcomes (2)

• Safety as measured by grade and frequency of adverse events

  Adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  30 days after completion of treatment

• Maximum Tolerated Dose (MTD) as measured by the number of dose-limiting toxicities in each dose level (cohort)

  MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached.

  Completion of the first cycle for all participants in dose expansion phase (approximately 12 months)

Secondary Outcomes (4)

• Objective response rate as measured by CD30 expression

  Up to 2 years after discontinuation of treatment

• Overall response rate

  Up to 2 years after discontinuation of treatment

• Duration of response

  Up to 2 years after discontinuation of treatment

• Progression-free survival (PFS)

  Up to 2 years after discontinuation of treatment

Study Arms (3)

Starting Dose (brentuximab vedotin & lenalidomide)

EXPERIMENTAL

Brentuximab vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.

Drug: Brentuximab vedotin; Drug: Lenalidomide

Dose Level 1 (brentuximab vedotin & lenalidomide)

EXPERIMENTAL

Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.

Drug: Brentuximab vedotin; Drug: Lenalidomide

Dose Level 2 (brentuximab vedotin & lenalidomide)

EXPERIMENTAL

Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle. Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.

Drug: Brentuximab vedotin; Drug: Lenalidomide

Interventions

Brentuximab vedotin DRUG

Also known as: Adcetris®

Dose Level 1 (brentuximab vedotin & lenalidomide); Dose Level 2 (brentuximab vedotin & lenalidomide); Starting Dose (brentuximab vedotin & lenalidomide)

Lenalidomide DRUG

Also known as: Revlimid®

Dose Level 1 (brentuximab vedotin & lenalidomide); Dose Level 2 (brentuximab vedotin & lenalidomide); Starting Dose (brentuximab vedotin & lenalidomide)

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory de novo or transformed DLBCL disease following at least one prior systemic therapy (for DLBCL).
• CD30 immunohistochemical staining using the anti-CD30 BerH2 antibody must be available on the most recent biopsy specimen. During dose escalation, patients can be either CD30 positive or CD30 negative. During dose expansion, 15 patients must be CD30 positive and 15 patients must be CD30 negative.
• Post-ASCT or not a candidate for ASCT. Prior allogeneic stem cell transplant is allowed if patient is off all immunosuppressives and has no evidence of active GVHD.
• Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV. Patients must be at least 3 months from the last dose of BV.
• Bidimensional measurable disease of at least 1.5 cm in the greatest transverse diameter as documented by CT or PET/CT.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Bone marrow and organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1,000/mcl
• Platelets ≥ 50,000/mcl
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) OR serum bilirubin ≤ 3.0 x IULN for patients with Gilbert's disease or documented hepatic involvement with NHL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x IULN OR ALT and AST ≤ 5.0 x IULN for patients with documented hepatic involvement with NHL
• Creatinine clearance ≥ 60 mL/min/1.73 m2 as calculated by Cockcroft-Gault
• Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS® program material. This is defined as either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last doses of brentuximab vedotin and lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• All study participants must be registered into the mandatory Revlimid REMS® program and be willing to comply with its requirements. Per standard Revlimid REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS® program.

You may not qualify if:

• Primary mediastinal B-cell lymphoma
• A history of other primary invasive malignancy that has not been in remission for at least 3 years or a current diagnosis of myelodysplastic syndrome (MDS) or an immature leukemia such as acute myeloid leukemia (AML).
• Known active cerebral/meningeal lymphoma.
• Present or history of progressive multifocal leukoencephalopathy (PML).
• NYHA Class III or IV congestive heart failure.
• Active CTCAE version 4.03 grade 3 or higher viral, bacterial, or fungal infection.
• Known to be positive for hepatitis B by surface antigen expression and hepatitis B core antibody.
• Known to have active hepatitis C infection (positive by polymerase chain reaction) or on antiviral therapy for hepatitis C within 6 months prior to the first doses of brentuximab vedotin and lenalidomide.
• Known to be positive for HIV.
• Receiving chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed at least 3 weeks prior to study entry, unless underlying disease is progressing on therapy.
• Currently receiving any other investigational agents.
• Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or lenalidomide.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide.
• Receiving immunosuppressive therapy.
• Refractory to prior therapy with brentuximab vedotin (evidence of progression within 30 days of the last dose).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Celgene: collaborator
• Seagen Inc.: collaborator

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Ohio State University, James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Ward JP, Berrien-Elliott MM, Gomez F, Luo J, Becker-Hapak M, Cashen AF, Wagner-Johnston ND, Maddocks K, Mosior M, Foster M, Krysiak K, Schmidt A, Skidmore ZL, Desai S, Watkins MP, Fischer A, Griffith M, Griffith OL, Fehniger TA, Bartlett NL. Phase 1/dose expansion trial of brentuximab vedotin and lenalidomide in relapsed or refractory diffuse large B-cell lymphoma. Blood. 2022 Mar 31;139(13):1999-2010. doi: 10.1182/blood.2021011894.

  PMID: 34780623 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Brentuximab Vedotin; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; 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)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nancy Bartlett, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 11, 2014
• First Posted: March 13, 2014
• Study Start: September 18, 2014
• Primary Completion: June 9, 2017
• Study Completion: January 12, 2022
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)