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


Original post, click here

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, pralatrexate, and romidepsin (Arm A); durvalumab, oral 5-azacitidine, and romidepsin (Arm B); durvalumab and romidepsin (Arm C); or durvalumab and oral 5-azacitidine (Arm D), in patients with relapsed or refractory (R/R) 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 combination s 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.

Primary Outcome Measures:

Secondary Outcome Measures:

  • Overall Response Rate (ORR) [ Time Frame: 1 year ]

    ORR will be defined as the sum of complete response rate and partial response rate based on evaluation of best response in each patient.

  • Duration of Response (DoR) [ Time Frame: 1 year ]

    Time from documentation of tumor response to disease progression

  • Progression Free Survival (PFS) [ Time Frame: 1 year ]

    Time from study treatment until disease progression or death

Estimated Enrollment: 45
Anticipated Study Start Date: June 15, 2017
Estimated Study Completion Date: June 30, 2020
Estimated Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)
Arm A

durvalumab, pralatrexate, and romidepsin

Drug: Durvalumab

Durvalumab is an investigational human monoclonal antibody that works to inhibit (block) a protein called PD-L1. Durvalumab has not been approved by the FDA for treatment of PTCL, but has been given to patients other types of cancers. Given intravenously (through the vein).

Other Name: MEDI4736

Drug: Pralatrexate

Pralatrexate is an anti-metabolite drug. Pralatrexate alone is FDA-approved for the treatment of PTCL. Given intravenously (through the vein).

Other Name: Folotyn

Drug: Romidepsin

Romidepsin is another type of chemotherapy known as HDAC (histone deacetylase) inhibitors. Romidepsin has not been approved for use in lymphoma other than CTCL by the FDA. Given intravenously (through the vein).

Other Name: Depsipeptide

Arm B

durvalumab, oral 5-azacitidine, and romidepsin

Drug: Durvalumab

Durvalumab is an investigational human monoclonal antibody that works to inhibit (block) a protein called PD-L1. Durvalumab has not been approved by the FDA for treatment of PTCL, but has been given to patients other types of cancers. Given intravenously (through the vein).

Other Name: MEDI4736

Drug: Romidepsin

Romidepsin is another type of chemotherapy known as HDAC (histone deacetylase) inhibitors. Romidepsin has not been approved for use in lymphoma other than CTCL by the FDA. Given intravenously (through the vein).

Other Name: Depsipeptide

Drug: Oral 5-Azacitidine

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).

Other Name: Vidaza

Arm C

durvalumab and romidepsin

Drug: Durvalumab

Durvalumab is an investigational human monoclonal antibody that works to inhibit (block) a protein called PD-L1. Durvalumab has not been approved by the FDA for treatment of PTCL, but has been given to patients other types of cancers. Given intravenously (through the vein).

Other Name: MEDI4736

Drug: Romidepsin

Romidepsin is another type of chemotherapy known as HDAC (histone deacetylase) inhibitors. Romidepsin has not been approved for use in lymphoma other than CTCL by the FDA. Given intravenously (through the vein).

Other Name: Depsipeptide

Arm D

durvalumab and oral 5-azacitidine

Drug: Durvalumab

Durvalumab is an investigational human monoclonal antibody that works to inhibit (block) a protein called PD-L1. Durvalumab has not been approved by the FDA for treatment of PTCL, but has been given to patients other types of cancers. Given intravenously (through the vein).

Other Name: MEDI4736

Drug: Oral 5-Azacitidine

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).

Other Name: Vidaza

The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive lymphoid neoplasms and account for 10-15% of all newly diagnosed cases of non-Hodgkin’s lymphoma (NHL). The current prevalence of PTCL in the United States is estimated to be approximately 9,500 patient. Treatment options for patients with relapsed/refractory (R/R) PTCL have been limited. This study focuses on exploring rational combinations of these T-cell active agents in an effort to develop novel treatment platforms.