What side effects are associated with this type of intervention?

Common treatments for T-Cell Lymphoma include chemotherapy agents such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP regimen), as well as targeted therapies like brentuximab vedotin and histone deacetylase (HDAC) inhibitors. Known side effects of these treatments can include myelosuppression, neuropathy, fatigue, nausea, vomiting, and increased risk of infections. For treatments similar to CDK9 inhibitors, such as other kinase inhibitors, side effects may include gastrointestinal disturbances, liver enzyme abnormalities, and hematologic toxicities like neutropenia and thrombocytopenia.

What prior FDA approvals exist?

FDA-approved treatments for T-Cell Lymphoma include several targeted therapies and chemotherapeutic agents. Notable drugs include pralatrexate (Folotyn), a folate analog metabolic inhibitor, and romidepsin (Istodax), a histone deacetylase inhibitor. Additionally, brentuximab vedotin (Adcetris), an antibody-drug conjugate targeting CD30, is approved for certain types of T-Cell Lymphoma. While specific CDK9 inhibitors like PRT2527 are still under investigation, these approved treatments represent the current landscape of targeted therapies for T-Cell Lymphoma.

What other types of research exist?

Promising novel alternatives to PRT2527 for T-Cell Lymphoma patients include LY2835219 (a CDK4/6 inhibitor) and Ku0063794 (a dual mTORC1/2 inhibitor). LY2835219 has shown efficacy in inducing cell-cycle arrest and tumor growth inhibition in preclinical models. Ku0063794 has demonstrated effectiveness in inhibiting key signaling proteins and reducing cell viability in renal cell carcinoma models, which may translate to potential benefits in T-Cell Lymphoma.

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Cyclin-dependent kinase 9 inhibitor

PRT2527 + Zanubrutinib for Blood Cancers

Phase 1

Recruiting

Research Sponsored by Prelude Therapeutics

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline through approximately 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called PRT2527, which blocks a protein that helps cancer cells grow, in patients with certain blood cancers that have come back or did not respond to other treatments. It also tests PRT2527 in combination with another drug, zanubrutinib, which blocks a different protein involved in cancer growth. The goal is to find a safe and effective dose for these drugs.

Who is the study for?

This trial is for adults with certain aggressive blood cancers like B-cell lymphoma, mantle cell lymphoma, or chronic leukemia that have stopped responding to standard treatments. Participants must be in good physical condition (ECOG 0 or 1), able to follow the study plan, and have proper organ function. They can't join if they've had recent cancer treatment that conflicts with the study drugs, severe heart issues, lung disease with low oxygen levels, or a history of other cancers except some skin and localized cancers.

What is being tested?

The trial is testing PRT2527 alone and combined with Zanubrutinib in patients who have relapsed or refractory hematologic malignancies. It's a Phase 1 study focusing on finding the safest dose that works (PR2D) while checking how well these treatments work against these types of blood cancers.

What are the potential side effects?

Possible side effects include those common to cancer therapies such as fatigue, nausea, diarrhea; specific risks related to PRT2527 might involve changes in liver enzymes indicating liver stress. Zanubrutinib may cause bleeding problems, infections due to low white blood cell counts, high blood pressure and second primary malignancies.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through approximately 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through approximately 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through approximately 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

Dose limiting toxicity (DLT) of PRT2527

Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax

Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: AEs, CTCAE Assessments

Secondary study objectives

Anti-tumor activity of PRT2527 as monotherapy and in combination with zanubrutinib or venetoclax: Objective response rate (ORR)

Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Duration of response/Complete Response (DOR/DoCR)

Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Area under the curve

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: PRT2527/Zanubrutinib Combination in Lymphoid MalignanciesExperimental Treatment2 Interventions

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication specific cohort during the dose confirmation phase. Zanubrutinib will be administered orally as combination therapy once or twice daily.

Group II: PRT2527/Venetoclax Combination in Myeloid MalignanciesExperimental Treatment2 Interventions

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication specific cohort during the dose confirmation phase. Venetoclax will be administered orally as a combination therapy once daily.

Group III: PRT2527 Monotherapy in Myeloid MalignanciesExperimental Treatment1 Intervention

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication-specific cohorts during the dose confirmation phase.

Group IV: PRT2527 Monotherapy in Lymphoid MalignanciesExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

2019

Completed Phase 3

~2240

PRT2527

2022

Completed Phase 1

~30

Zanubrutinib

2017

Completed Phase 3

~2160

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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

Cyclin-Dependent Kinase (CDK) inhibitors, such as CDK9 inhibitors like PRT2527, function by blocking the activity of CDKs, which are essential for cell cycle progression and transcription regulation. In T-Cell Lymphoma, these inhibitors can stop the proliferation of cancerous cells and induce apoptosis by disrupting the transcription of genes necessary for tumor growth and survival. This mechanism is crucial for patients with relapsed or refractory T-Cell Lymphoma, as it offers a targeted therapeutic strategy to manage the disease.