Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Lymphoma, Large B-Cell, Diffuse

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Hodgkin Disease

Lymphoma, B-Cell

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Hodgkin Lymphoma

Participants will be sequentially enrolled at progressively higher dose levels to receive GS-9820 administered twice a day. Escalation will proceed to the maximum tolerated dose (MTD), defined as the highest tested dose associated with a rate of dose-limiting toxicities (DLT) of \< 33% during the first 4 weeks of therapy.

GS-9820 tablets containing 200 mg of GS-9820 administered orally

GS-9820

Henry Adewoye, MD

This study is to determine the appropriate dosing regimen of GS-9820 in subjects with lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.

A Phase 1b Study Evaluating GS-9820 in Subjects With Lymphoid Malignancies

A Phase 1b Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GS-9820 in Subjects With Lymphoid Malignancies

MTD will be assessed to determine the appropriate dosing regimens for use in future clinical trials of GS-9820 in subjects with lymphoid malignancies.

Overall safety will be assessed by overall safety profile, enumeration and description of any dose-limiting toxicities, serious adverse events, or adverse events leading to discontinuation of study drug.

* Cmax is defined as the maximum concentration of drug
* Tmax is defined as the time of Cmax
* Ctrough is defined as the trough concentration
* AUC is defined as the area under the plasma concentration versus time curve

Tumor control as assessed by overall response rate (ORR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), percent change in lymph node area, lymph node response rate, splenomegaly response rate, ALC response rate, hepatomegaly response rate, platelet response rate, hemoglobin response rate, and neutrophil response rate.

Drug administration for GS-9820 as assessed by prescribing records and GS-9820 compliance as assessed by quantification of used and unused drug.

Gilead Sciences

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Peripheral T-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Romidepsin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Copanlisib and romidepsin will be both administered via IV (through a vein in arm) on days 1, 8, and 15 every 28 days, also called a "cycle".

Novel, pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with potent activity against both the δ and α isoforms9. Copanlisib has been evaluated for the treatment of a wide variety of malignancies, including lymphoma, either as a single agent or in combination with other investigational agents.

Copanlisib

Indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

Changchun Deng, MD, PhD

This is an open label, Phase IB dose-escalation study of the PI3K inhibitor copanlisib in combination with romidepsin in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL).

The primary objective of the phase I study is to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and dose limiting toxicities (DLTs) of the combination of copanlisib and romidepsin in patients with R/R, NHL or HL.

The non-Hodgkin lymphomas (NHL) represent 4-5% of all new cancer cases, and is the seventh leading cause of cancer death. In 2015, there were an estimated 71,850 cases in the United States, and approximately 19,790 deaths. An evaluation of the distribution of NHL sub-types was performed on 114,548 cases of lymphoid neoplasms diagnosed between 1992-2001 and reported to the Surveillance Epidemiology and End Results (SEER) registry. Of all NHL, 87,666 were B-cell lymphoid neoplasms, and 6,228 were considered T/Natural Killer (NK) cell neoplasms.

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 NHL. The current prevalence of PTCL in the United States is estimated to be approximately 9,500 patients. PTCL-Not Otherwise Specified (NOS), a nodal subtype, is the most common T-cell lymphoma in the United States and Europe. PTCL is associated with a significantly worse prognosis compared to its B-cell counterparts. Treatment options for patients with relapsed/refractory (R/R) PTCL have been limited. The addition of novel drugs to conventional chemotherapy has largely proven unsuccessful. Since 2009, new drugs have entered the therapeutic field for patients with R/R PTCL.

Pralatrexate was the first drug approved for patients with R/R PTCL. Other drugs approved for patients with R/R PTCL include romidepsin and belinostat. These agents appear to exhibit lineage-specific activity in PTCL. Over the past few years, the investigators have focused on exploring rational combinations of these T-cell active agents in an effort to develop novel treatment platforms. Early clinical studies of these combinations have shown very promising activity.

Copanlisib in Combination With Romidepsin in Patients With Relapsed or Refractory Mature T-cell Lymphoma

Phase 1B Study of the PI3K Inhibitor Copanlisib in Combination With Romidepsin in the Treatment of Patients With Relapsed or Refractory Mature T-cell Lymphoma

The estimated MTD would be the highest dose at which 0 out of 3 or 1 out of 6 subjects experience a dose-limiting toxicity (DLT), i.e. dose with an observed DLT rate of less than 0.33.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase 1b Study Evaluating GS-9820 in Subjects With Lymphoid Malignancies	NCT01705847	Lymphoid Malign...	GS-9820	18 Years -	Gilead Sciences
Copanlisib in Combination With Romidepsin in Patients With Relapsed or Refractory Mature T-cell Lymphoma	NCT04233697	Lymphoma, T-Cel...	Copanlisib Romidepsin	18 Years -	Columbia University

Spots Global Cancer Trial Database for hodgkin lymphoma (hl)