Duvelisib in Combination With BMS-986345 in Lymphoid Malignancy

NCT05065866 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCC-21096
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to find a safe dose and to evaluate the safety and tolerability of the drug BMS-986345, in combination with duvelisib.

Conditions

Non Hodgkin Lymphoma; Hodgkin Lymphoma; Myeloma; Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Maximum Tolerated Dose (MTD) of BMS-986345 in combination with Duvelisib in patients with lymphoid malignancy. The MTD is defined as the highest dose with an observed incidence of dose limiting toxicity (DLT) in no more than one out of six patients treated at a particular dose level.

  Up to 26 months

Secondary Outcomes (4)

• Overall Response

  at 3 and 12 months

• Duration of Response

  Up to 24 months

• Overall Survival

  Up to 26 months

• Progression Free Survival (PFS)

  Up to 26 months

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Dose escalation to determine the maximum tolerated dose (MTD) of BMS-986345 in combination with Duvelisib in patients with lymphoid malignancy. Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A total of 6 dose levels will be used.

Drug: BMS-986345; Drug: Duvelisib

Interventions

BMS-986345 DRUG

Patients will be treated at the following dose levels: Duvelisib BMS-986345 Dose Level 15 mg twice daily 100mg daily -1 25 mg twice daily 100mg daily 1 50 mg twice daily 100mg daily 2 75 mg twice daily 100mg daily 3 75 mg twice daily 200mg daily 4 75 mg twice daily 300mg daily 5 After the first two cycles of treatment, the dose of Duvelisib will be dropped to 25 mg twice daily irrespective of the starting dose level unless the patient is at dose level -1 then they will stay on that dose level after the initial 2 cycles

Also known as: Oral Azacitidine

Dose Escalation

Duvelisib DRUG

Patients will be treated at the following dose levels: Duvelisib BMS-986345 Dose Level 15 mg twice daily 100mg daily -1 25 mg twice daily 100mg daily 1 50 mg twice daily 100mg daily 2 75 mg twice daily 100mg daily 3 75 mg twice daily 200mg daily 4 75 mg twice daily 300mg daily 5 After the first two cycles of treatment, the dose of Duvelisib will be dropped to 25 mg twice daily irrespective of the starting dose level unless the patient is at dose level -1 then they will stay on that dose level after the initial 2 cycles

Also known as: Copiktra

Dose Escalation

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 histologically proven diagnosis of lymphoid malignancy according to World health organization (WHO) defined as:
• a. Mature T cell lymphoma: (i) Peripheral T-Cell lymphoma not otherwise specified (PTCL, NOS) (ii) Anaplastic large T cell lymphoma, ALK +ve (ALCL ALK+) (iii) Anaplastic large T cell lymphoma, ALK +ve (ALCL ALK-) (iv) Angioimmunobastic T cell lymphoma (AITL) (v) Enteropathy associated T-cell lymphoma ((EATL) (vi) Estranodal NK T cell lymphoma (ENKTL) b. T-cell Prolymphocytic leukemia c. Aggressive NK-cell leukemia d. Adult T-cell leukemia/lymphoma e. Hepatosplenic T-cell lymphoma f. Primary cutaneous T cell lymphoma: (i) Mycosis fungoides (ii) Primary cutaneous CD30+ve T cell lymphoproliferative disorder (iii) Primary cutaneous peripheral T cell lymphoma, NOS (iv) Subcutaneous panniculitis-like T-cell lymphoma (v) Primary cutaneous gamma/delta T cell lymphoma (vi) Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma g. Mantle cell lymphoma h. Diffuse large B cell lymphoma, NOS i. Primary mediastinal large B cell lymphoma j. High grade B cell lymphoma, NOS k. High grade B cell lymphoma with myc and bcl2 and/or bcl6 rearrangements
• Disease specific eligibility:
• Mature T cell lymphoma, T cell prolymphocytic leukemia, aggressive NK-cell leukemia, adult T-cell leukemia/lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T cell lymphoma, primary cutaneous gamma/delta T cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma: Patient must have progressed after one line of therapy and ineligible for hematopoietic stem cell transplantation ,or progressed on two lines of therapy with no available curative options per investigator discretion.
• Mantle cell lymphoma: Patients must have progressed after at least two line of therapy with no available options that would provide clinical benefit per investigator discretion. Patients with prior Chimeric Antigen Receptor T cell (CART cells) therapy are allowed .
• Diffuse large B cell lymphoma NOS, primary mediastinal large B cell lymphoma, high grade B cell lymphoma NOS, high grade B cell lymphoma with myc, bcl2 and/or bcl6 rearrangements: Patients must have progressed on at least two lines of therapy with no available options that would provide clinical benefit per investigator discretion. Patients with prior Chimeric Antigen Receptor T cell (CART cells) therapy are allowed.
• Patients must have measurable disease with a lymph node or tumor mass \> 1.5 cm in at least one dimension as assessed by computed tomography (CT)
• Patients must be ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (corresponds to Karnofsky Performance Status \[KPS\] ≥ 80%).
• Patients must have adequate organ and marrow function as defined in protocol.
• Willingness to avoid pregnancy or fathering children based on the following criteria: a. Woman of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 45 years of age). b. Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed.
• c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through at least 93 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy

You may not qualify if:

• History of central nervous system lymphoma (either primary or metastatic).
• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment.
• Active graft-versus-host disease
• Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \>20 mg of prednisone (or equivalent) once daily (QD)
• Receipt of anticancer medications or investigational drugs within the following intervals before the first dose of study treatment:a. \< 6 weeks for mitomycin-C or nitrosoureas.b. \< 4 weeks for immunotherapy.c. \< 3 weeks for radiotherapy. d. \< 2 weeks for any investigational agent or other anticancer medications or equal to 5 half lives of the investigational drug, whichever is longer.
• Prior CART cells therapy within 90 days of enrollment or if they have not recovered from CART cells therapy toxicity to grade 1 or less.
• Inadequate recovery from toxicity and/or complications from a major surgery before the date of the first dose of study treatment.
• Prior treatment-related toxicities have not resolved to NCI CTCAE v5 ≤ Grade 1 before the date of the first dose of study treatment except for stable chronic toxicities (Grade ≤ 2) not expected to resolve (eg, stable Grade 2 peripheral neurotoxicity).
• Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
• Use or expected use during the study of any prohibited medications, including potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the date of study treatment administration (see appendix 11.1) in addition to excluding patients on CYP3A inducers.
• Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
• Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without PI approval.
• History of stroke or intracranial hemorrhage within 6 months of the date of study treatment administration.
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of study treatment.
• Known HIV infection or positivity on immunoassay.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Secura Bio, Inc.: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease; Neoplasms, Plasma Cell; Leukemia, Lymphoid

Interventions

Azacitidine; duvelisib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Hayder Saeed, MD

  Moffitt Cancer Center

  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 23, 2021
• First Posted: October 4, 2021
• Study Start: November 18, 2021
• Primary Completion: January 2, 2024
• Study Completion: April 24, 2024
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

US (1)