Duvelisib Exposure to Enhance Immune Profiles of T Cells in Patients With Recurrent or Refractory Diffuse Large B-Cell Lymphoma, DEEP T CELLS Study

NCT04890236 | Completed Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00001001NCI-2020-06380Winship5085-20P30CA138292
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

This early phase I trial investigates how well duvelisib exposure before CAR-T cell manufacturing works to enhance immune profiles of T cells in patients with diffuse large B-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Duvelisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, may favorably change a patient's T cells to make them more efficient and have a longer duration for manufacturing of CAR-T cells.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Fold-change increase in CD27/CD28 double positive T cells

  Will estimate fold-change increase in CD27/CD28 double positive T cells following in vivo exposure to duvelisib using multiparametric flow cytometry.

  From Baseline up to day 15

Secondary Outcomes (6)

• Proportion of patients that completed at least 75% of duvelisib doses

  Up to day 15

• Manufacturing time of CAR-T 19 cells

  Up to day 15

• Change in proportion of CD27/28 double positive T cells and CD4/8 double negative T cells

  At baseline and at day 15

• Overall response rate (ORR)

  At 3 months following CAR-T cell infusion

• Frequency of intensive care unit (ICU) transfers due to cytokine release syndrome (CRS) and/or neurotoxicity

  Up to day 90 post CAR-T cell infusion

Study Arms (1)

Treatment (duvelisib)

EXPERIMENTAL

Patients receive duvelisib PO BID for 2 weeks prior to collection of CAR-T cells in the absence of disease progression or unacceptable toxicity. Patients then receive tisagenlecleucel via infusion.

Drug: Duvelisib; Biological: Tisagenlecleucel

Interventions

Duvelisib DRUG

Given PO

Also known as: 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, Copiktra, INK-1197, IPI-145

Treatment (duvelisib)

Tisagenlecleucel BIOLOGICAL

Given via infusion

Also known as: CART-19, CART19, CTL019, CTL019 T-cells, Kymriah, Tisagenlecleucel-T

Treatment (duvelisib)

Eligibility Criteria

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

You may qualify if:

• Patients must have a biopsy proven diagnosis of relapsed/refractory diffuse large B-cell lymphoma (DLBCL)
• Eastern Cooperative Oncology Group (ECOG) \< 2
• Serum creatinine (Cr) \< 2.0 mg/dL
• Alanine aminotransferase (AST)/aspartate aminotransferase (ALT) \< 2 x upper limit of normal (ULN)
• Total bilirubin \< 2.0 mg/dL
• Hemoglobin \> 8 g/dL
• Platelet count \> 50 K/mcl
• An absolute neutrophil count (ANC) \> 1,000/mm\^3
• An absolute lymphocyte count (ALC) \> 300/mm\^3
• Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of their DLBCL \>= 2 weeks before the start of duvelisib. There is no limit on how many previous lines of treatment a patient may have received
• The effects of duvelisib on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test prior to starting therapy. WOCBP and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) from enrollment into this study until at least 12 months after tisagenlecleucel infusion and until CAR-T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests (qPCR tests will be available upon request). A woman of childbearing potential (WOCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use highly effective contraception prior to the study, for the duration of study participation, and 3 months after completion of duvelisib administration. WOCBP must have a negative pregnancy test within 24 hours of leukapheresis, lymphodepletion (if performed) and tisagenlecleucel infusion (if lymphodepletion not performed)
• The patient must be willing to comply with fertility requirements as below:
• Total abstinence (when this is in line with the usual practice and lifestyle of the patient). Periodic abstinence (i.e, calendar, ovulation, post-ovulation methods) and withdrawals are not acceptable forms of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without a hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone assessment
• Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner

You may not qualify if:

• Primary central nervous system lymphoma
• Patients with central nervous system (CNS) involvement of lymphoma
• History of autoimmune disease, including but not limited to:
• Inflammatory bowel diseases (Crohn's disease, ulcerative colitis, celiac disease)
• Systemic lupus erythematosus
• Grave's disease
• Myasthenia gravis
• Rheumatoid arthritis
• Wegner's syndrome
• Patients with history of drug reaction and eosinophilia systemic syndrome (DRESS) or toxic epidermal necrolysis (TEN)
• History of human immunodeficiency virus (HIV), active Hepatitis C Infection or active Hepatitis B infection as defined by:
• Patients with a positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV Ab) will be excluded
• Patients with a positive hepatitis B core antibody (HBcAb) must have negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) to be eligible and must be periodically monitored for HBV reactivation by institutional guidelines
• Patients with known active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects with detectable viral load)
• Patients with ongoing treatment for systemic bacterial, fungal or viral infection

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• Secura Bio, Inc.: collaborator
• Novartis: collaborator

Study Sites (2)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

duvelisib; tisagenlecleucel; CTL019 chimeric antigen receptor

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

Study Officials

• Edmund K Waller, MD, PhD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 18, 2021
• Study Start: January 13, 2022
• Primary Completion: March 20, 2024
• Study Completion: September 4, 2024
• Last Updated: January 20, 2025

Record last verified: 2025-01

Locations

US (2)