Durvalumab in Different Combinations With Pralatrexate, Romidepsin and Oral 5-Azacitidine for Lymphoma

Part of paid clinical trials in Charlottesville, Virginia.

Sponsor
University of Virginia
Study ID
NCT03161223
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Lymphoma, T-Cell

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    Durvalumab is an investigational human monoclonal antibody that works to inhibit (block) a protein called programmed cell death-1 ligand 1 (PD-L1). Durvalumab has not been approved by the FDA for the treatment of PTCL but has been given to patients other types of cancers. Given intravenously (through the vein). Starting dose: 1500 mg
  • Pralatrexate — DRUG
    Pralatrexate is an antimetabolite drug. Pralatrexate alone is FDA-approved for the treatment of PTCL. Given intravenously (through the vein). Starting dose: 25 mg/m2
  • Romidepsin — DRUG
    Romidepsin is another type of chemotherapy known as histone deacetylase (HDAC) inhibitors. Romidepsin has not been approved for use in lymphoma other than Cutaneous T cell lymphoma (CTCL) by the FDA. Given intravenously (through the vein). Starting dose: 12 mg/m2
  • 5-Azacitidine — DRUG
    Oral 5-azacitidine is used for the treatment of myelodysplastic syndrome and acute myeloid leukemia. Azacitidine prevents the body from making DNA and RNA that cells need to grow. This stops the growth of cancer cells and causes them to die. Given by mouth (orally). Starting dose: 300 mg daily

Study Details

This is an open-label, Phase 1/2a, dose-finding study with an initial phase 1 portion, articulated in four separate treatment arms, followed by a dedicated phase 2 for qualifying treatment Arm(s). The primary objective of the Phase 1 portion is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of: Durvalumab, oral 5-azacitidine, and romidepsin (Arm A); durvalumab, pralatrexate, and romidepsin (Arm B); durvalumab and romidepsin (Arm C); or durvalumab and oral 5-azacitidine (Arm D), in patients with peripheral T-cell lymphoma (PTCL). The safety and toxicity profile of these combinations will be evaluated throughout the entire study. If one or more of the combinations in Arms A, B, C, or D are found to be feasible and an MTD is established, the phase 2 portion of the study will be initiated for the combination(s) with the strongest efficacy signal provided acceptable toxicity.

Key Dates

Start date
May 30, 2018
Status verified
Mar 2022
Primary completion
Feb 28, 2023
Completion
Feb 28, 2023

Study Design

Enrollment
148 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Other: A: Oral 5-azacitidine, durvalumab, romidepsin
    Arm A: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase), durvalumab will be administered intravenously on day 8 and romidepsin intravenously on days 8 and 15 of a 28-day treatment cycle
  • Other: B: durvalumab, pralatrexate, romidepsin
    Arm B: Durvalumab will be administered intravenously on day 1, pralatrexate will be administered intravenously on days 1 and 15, and romidepsin will be administered intravenously on days 1 and 15. Each treatment cycle will last 28 days. All patients receiving pralatrexate will receive folic acid and vitamin B12 supplementation according to the drug package insert. Leucovorin rescue is also allowed at the dose of 15 mg orally twice daily on days 3 to 6 and 17 to 20.
  • Other: C: durvalumab, romidepsin
    Arm C: Durvalumab will be administered intravenously on day 1 and romidepsin will be administered intravenously on days 1, 8, and 15 of a 28-day treatment cycle
  • Other: D: durvalumab, 5-azacitidine
    Arm D: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase) and durvalumab will be administered intravenously on day 8 of a 28-day treatment cycle

Primary Outcome Measure

Maximum Tolerated Dose (MTD) [ Time Frame: 1 year ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of VirginiaCharlottesvilleVirginia22903
Abdelmalek Marian
Enrica Marchi, M.D., PhD (PRINCIPAL_INVESTIGATOR)

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University of Virginia· Charlottesville, VA

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