70 Participants Needed

Ruxolitinib + Duvelisib for Lymphoma

Recruiting at 8 trial locations
AM
Steven M. Horwitz, MD - MSK Lymphoma ...
Overseen BySteven M. Horwitz, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This study will test the safety of ruxolitinib, given at one dose that does not change, and duvelisib, given at different doses, to find out what effects, if any, the study treatment has on people with relapsed or refractory NK-cell or T-cell lymphoma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you may need to stop using certain medications that strongly affect liver enzymes (CYP3A) at least 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Ruxolitinib and Duvelisib for treating lymphoma?

Duvelisib has been shown to be effective in treating certain types of lymphoma, such as chronic lymphocytic leukemia and follicular lymphoma, especially after other treatments have failed. It works by blocking specific proteins that help cancer cells grow. Additionally, studies suggest that combining duvelisib with other drugs can enhance its effectiveness in fighting cancer.12345

Is the combination of Ruxolitinib and Duvelisib safe for humans?

Ruxolitinib is generally well tolerated, but common side effects include mild to moderate anemia (low red blood cell count), thrombocytopenia (low platelet count), and lymphopenia (low white blood cell count), which are usually manageable with dosage adjustments. Rarely, it can cause skin reactions. There is no specific safety data available for the combination with Duvelisib, but these findings provide some insight into the safety of Ruxolitinib alone.678910

What makes the drug combination of Ruxolitinib and Duvelisib unique for treating lymphoma?

The combination of Ruxolitinib and Duvelisib is unique because Ruxolitinib targets the JAK-STAT pathway, which is often overactive in certain lymphomas, potentially enhancing the effectiveness of treatment by inducing cancer cell death and inhibiting tumor growth.1112131415

Research Team

Alison J. Moskowitz, MD - MSK Lymphoma ...

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with certain types of T-cell lymphoma or leukemia, who've had at least one prior therapy (treatment-naive allowed for some conditions), can join this trial. They must be able to swallow pills, have a specific level of organ function, and not be pregnant or breastfeeding. Contraception is required during the study.

Inclusion Criteria

My lymphoma is a type of T-cell lymphoma confirmed by tests.
I have a specific type of T-cell lymphoma.
I can take care of myself but might not be able to do heavy physical work.
See 6 more

Exclusion Criteria

I am currently being treated for another type of cancer.
I have had surgery or a condition that affects how drugs are absorbed in my body.
Specific criteria for patients with HIV infection or chronic hepatitis B or C
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib and duvelisib with dose-escalation to determine safety and optimal dosing

8 weeks
Regular visits for safety assessments

Cohort Expansion

Further expansion for patients with T-PLL and TFH lymphomas to evaluate disease control rate

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • Duvelisib
  • Ruxolitinib
Trial Overview The trial tests Ruxolitinib at a fixed dose and Duvelisib at varying doses in people with relapsed/refractory NK-cell or T-cell lymphoma to determine their safety and effects.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Ruxolitinib and DuvelisibExperimental Treatment2 Interventions
Ruxolitinib 20mg BID plus Duvelisib 25mg, 50mg, or 75mg BID. Patients will be instructed to take duvelisib and ruxolitinib by mouth every 12 hours, the same time each day, +/- 2 hours. Duvelisib and ruxolitinib will be provided via the institutional investigational pharmacy. The researchers will utilize a dose-escalation standard 3+3 design in which we evaluate 3 doses of duvelisib (25mg BID, 50mg BID, and 75mg BID) in combination with ruxolitinib 20mg BID. A minus-1 dose level of duvelisib (15mg BID) can be used if de-escalation is needed. The cohort expansion phase will have two treatment groups JAK/STAT activation or mutation present or JAK/STAT activation or mutation absent or unknown. Upon discussion with PI, the treating physician may increase dose up to 20 mg of ruxotlinib and/or 25 mg of duvelisib when deemed clinically favorable. T-prolymphocytic leukemia (T-PLL) and T-follicular helper (TFH) lymphoma expansion: Further expansion for patients with T-PLL and TFH lymphomas.

Duvelisib is already approved in United States for the following indications:

🇺🇸
Approved in United States as Copiktra for:
  • Relapsed or refractory chronic lymphocytic leukemia (CLL)
  • Relapsed or refractory small lymphocytic lymphoma (SLL)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Findings from Research

Duvelisib is a dual inhibitor of PI3Kδ and PI3Kγ, approved by the FDA in 2018 for treating adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) after at least two prior therapies.
It has also received accelerated approval for relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, highlighting its efficacy in difficult-to-treat blood cancers.
Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases.Rodrigues, DA., Sagrillo, FS., Fraga, CAM.[2020]
Duvelisib, an oral dual inhibitor, showed a 47.3% overall response rate in a phase II trial involving 129 patients with indolent non-Hodgkin lymphoma (iNHL) who were refractory to previous treatments, indicating its efficacy as a new treatment option.
The treatment had a manageable safety profile, with common side effects including diarrhea and neutropenia, affecting a significant portion of patients, but overall it provided clinically meaningful activity for those with limited options.
DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma.Flinn, IW., Miller, CB., Ardeshna, KM., et al.[2020]
Duvelisib, a dual inhibitor of PI3Kδ and PI3Kγ, was tested on 30 pediatric acute lymphoblastic leukemia (ALL) patient-derived xenografts (PDXs) and was found to be well-tolerated, but showed limited efficacy with only one objective response despite reducing leukemia cells in some cases.
The study revealed no clear relationship between the drug's effectiveness and the expression or mutation status of PI3Kδ or PI3Kγ, indicating that duvelisib's action may not be dependent on these factors in the context of ALL.
In vivo activity of the dual PI3Kδ and PI3Kγ inhibitor duvelisib against pediatric acute lymphoblastic leukemia xenografts.Randall, J., Evans, K., Watts, B., et al.[2023]

References

Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases. [2020]
DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. [2020]
In vivo activity of the dual PI3Kδ and PI3Kγ inhibitor duvelisib against pediatric acute lymphoblastic leukemia xenografts. [2023]
The phosphoinositide-3 kinase (PI3K)-δ,γ inhibitor, duvelisib shows preclinical synergy with multiple targeted therapies in hematologic malignancies. [2023]
Duvelisib: First Global Approval. [2019]
Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. [2021]
Ruxolitinib versus standard therapy for the treatment of polycythemia vera. [2022]
Ruxolitinib: A Review in Polycythaemia Vera. [2021]
Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]
Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
Ruxolitinib significantly enhances in vitro apoptosis in Hodgkin lymphoma and primary mediastinal B-cell lymphoma and survival in a lymphoma xenograft murine model. [2019]
Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. [2023]
13.United Statespubmed.ncbi.nlm.nih.gov
Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]
Ruxolitinib: in the treatment of myelofibrosis. [2022]
Ruxolitinib for the treatment of primary myelofibrosis. [2021]