What side effects are associated with this type of intervention?

Romidepsin, a Histone Deacetylase Inhibitor, is commonly associated with side effects such as nausea, vomiting, fatigue, infections, and hematologic abnormalities like thrombocytopenia and neutropenia. Parsaclisib, a PI3K Inhibitor, may cause side effects including diarrhea, colitis, hyperglycemia, hypertension, and liver enzyme abnormalities. Both treatments require careful monitoring due to their potential for serious adverse effects.

What prior FDA approvals exist?

Romidepsin, a histone deacetylase inhibitor, has been approved by the FDA for the treatment of Cutaneous T-Cell Lymphoma (CTCL). Another histone deacetylase inhibitor, Vorinostat, is also FDA-approved for CTCL. While Parsaclisib, a PI3K inhibitor, is still under investigation, other PI3K inhibitors like Duvelisib have been approved for certain types of lymphomas, though not specifically for CTCL. These approvals highlight the ongoing exploration of targeted therapies in the treatment of CTCL.

What other types of research exist?

Promising novel alternatives for CTCL treatment in 2024 include Brentuximab Vedotin (an antibody-drug conjugate targeting CD30), Mogamulizumab (a monoclonal antibody targeting CCR4), and Pembrolizumab (a PD-1 inhibitor). These agents have shown efficacy in clinical trials and offer different mechanisms of action compared to Romidepsin and Parsaclisib.

← Back to Search

PI3K inhibitor

Romidepsin + Parsaclisib for Lymphoma

Phase 1

Waitlist Available

Led By John C Reneau, MD, PhD

Research Sponsored by Ohio State University Comprehensive Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 18 years

Biopsy proven diagnosis of PTCL or CTCL

Must not have

Prior treatment with a PI3K inhibitor

Clinically significant history of liver disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, parsaclisib and romidepsin, for patients with T-cell lymphomas that have returned or not responded to standard treatments. Romidepsin stops cancer cells from dividing, while parsaclisib blocks a pathway that helps cancer cells grow. The goal is to find the best dose and see how well this combination works in reducing cancer and improving patient survival.

Who is the study for?

Adults with relapsed or refractory T-cell lymphomas, including various subtypes like Anaplastic Large Cell and Cutaneous T-Cell Lymphoma. Participants must have a life expectancy of at least 90 days, adequate organ function, no recent cancer treatments (with some exceptions for steroids), and not be pregnant. They should agree to use effective contraception.

What is being tested?

The trial is testing the combination of Romidepsin and Parsaclisib to find the best dose for treating T-cell lymphomas that haven't responded well to other treatments. It aims to see if this combo can achieve complete remission or significant reduction in cancer size and improve patient survival.

What are the potential side effects?

Potential side effects include reactions related to immune system activation, liver enzyme changes, blood cell count variations which could affect infection risk or cause fatigue, gastrointestinal issues such as nausea or diarrhea, and possible heart rhythm abnormalities.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am 18 years old or older.

Select...

I have been diagnosed with PTCL or CTCL through a biopsy.

Select...

My cancer is at least stage IB and affects more than 10% of my body or is a type that has spread to my lymph nodes or other areas.

Select...

My condition is mycosis fungoides with large cell transformation.

Select...

I can take care of myself and perform daily activities.

Select...

My PTCL cancer returned or didn't respond after treatment, including brentuximab for ALCL.

Select...

My CTCL cancer has worsened after at least 2 skin treatments or 1 body-wide treatment.

Select...

My kidneys are functioning well, with a creatinine clearance rate of at least 50 mL/min.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with a PI3K inhibitor before.

Select...

I have a significant history of liver problems.

Select...

I have recently used medication that weakens my immune system.

Select...

My brain or spinal cord disease is not under control.

Select...

I cannot swallow pills or have major stomach problems.

Select...

I have not received a live vaccine in the last 30 days.

Select...

I am not taking strong CYP3A4 inhibitors or inducers.

Select...

I am currently taking medication for an infection.

Select...

My condition worsened while on romidepsin or soon after stopping it.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) of parsaclisib

Secondary study objectives

Disease control rate (DCR)

Duration of response (DOR)

Overall response rate (ORR)

+2 more

Side effects data

From 2021 Phase 1 & 2 trial • 88 Patients • NCT02018861

44%

Nausea

41%

Cough

41%

Diarrhoea

41%

Vomiting

33%

Fatigue

33%

Constipation

26%

Neutropenia

26%

Dizziness

22%

Arthralgia

22%

Headache

22%

Abdominal pain

19%

Thrombocytopenia

19%

Hypotension

15%

Dyspnoea

15%

Hypokalaemia

15%

Hypophosphataemia

15%

Oedema peripheral

15%

Oropharyngeal pain

15%

Upper respiratory tract infection

15%

Chills

15%

Back pain

15%

Tachycardia

15%

Anaemia

15%

Decreased appetite

11%

Sinusitis

11%

Aspartate aminotransferase increased

11%

Dehydration

11%

Hyperglycaemia

11%

Myalgia

11%

Palpitations

11%

Pruritus

11%

Stomatitis

11%

Electrocardiogram QT prolonged

11%

Muscle spasms

11%

Muscular weakness

11%

Night sweats

11%

Peripheral swelling

11%

Candida infection

11%

Dry skin

11%

Pneumonia

Urinary tract infection

Alanine aminotransferase increased

Anxiety

Blister

Hypoalbuminaemia

Neck pain

Pain

Pain in extremity

Pyrexia

Rash

Rash papular

Wheezing

Bronchitis

Abdominal distension

Nasal congestion

Platelet count decreased

Asthenia

Blood alkaline phosphatase increased

Dysgeusia

Fall

Insomnia

Nasopharyngitis

Weight increased

Contusion

Dermatitis exfoliative

Acute kidney injury

Confusional state

Leukocytosis

Mental status changes

Pleural effusion

Renal tubular necrosis

Respiratory failure

Syncope

Urinary incontinence

Abdominal discomfort

Herpes zoster

Hypercalcaemia

Hypertension

Paraesthesia

Respiratory tract congestion

Rhinorrhoea

Seasonal allergy

Taste disorder

Tinnitus

Transaminases increased

Upper-airway cough syndrome

White blood cell count decreased

Anal incontinence

Hip fracture

Malignant pleural effusion

Haematuria

Neuropathy peripheral

Neutrophil count decreased

Pain in jaw

Weight decreased

Bacteraemia

Gastritis erosive

Depression

Drug hypersensitivity

Erythema

Hyperhidrosis

Vaginal discharge

100%

80%

60%

40%

20%

Study treatment Arm

Parsaclisib 30 mg QD

Parsaclisib 20 mg QD

Parsaclisib 45 mg QD

Parsaclisib 20 mg QD + R-ICE

Parsaclisib 20 mg + Itacitinib 300 mg

Parsaclisib 30 mg + Itacitinib 300 mg

Total

Parsaclisib 15 mg QD + R-ICE

Parsaclisib 5 mg QD

Parsaclisib 10 mg QD

Parsaclisib 15 mg QD

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (romidepsin, parsaclisib)Experimental Treatment2 Interventions

PRE-PHASE: Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. INDUCTION PHASE: Patients receive romidepsin IV over 4 hours on days 1,8, and 15 and parsaclisib PO QD on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive romidepsin IV over 4 hours on days 1, 8, and 15 and parsaclisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Romidepsin

2011

Completed Phase 2

~790

Parsaclisib

2017

Completed Phase 2

~680

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Romidepsin, a Histone Deacetylase (HDAC) inhibitor, works by blocking HDAC enzymes, leading to the activation of tumor suppressor genes and inducing apoptosis in cancer cells. Parsaclisib, a PI3K inhibitor, blocks the PI3K pathway, which is essential for cancer cell growth and survival, thereby reducing tumor growth and promoting cancer cell death. These targeted mechanisms are crucial for Cutaneous T-Cell Lymphoma patients as they offer more precise and potentially effective treatment options by directly interfering with pathways critical for cancer cell survival and proliferation.