Ruxolitinib + CHOP for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Organ transplant, Cirrhosis, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new drug combination is safe and effective for individuals with untreated nodal T-follicular helper (TFH) cell lymphoma. The combination includes ruxolitinib, which blocks cancer cell growth, and a standard chemotherapy treatment known as CHOP (comprising cyclophosphamide, doxorubicin, and vincristine). Researchers seek to evaluate the effectiveness of this combination and identify any side effects. Individuals who have not yet received treatment for their nodal TFH cell lymphoma may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications or foods that strongly affect a specific liver enzyme (CYP3A) at least 2 weeks before starting the study. If you need to take certain medications for fungal infections during the trial, dose adjustments may be necessary.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ruxolitinib is generally well-tolerated in cancer treatments. One study found it safe for patients with Hodgkin lymphoma, a type of cancer. Although results varied, most patients managed the treatment well.

The CHOP chemotherapy regimen is a standard treatment for certain lymphomas, consisting of four drugs: cyclophosphamide, doxorubicin, vincristine, and prednisone. This combination is well-known and widely used in the medical field, demonstrating strong results in treating lymphomas. However, like many cancer treatments, it can cause side effects, such as tiredness or a weakened immune system.

This trial is in its early stages and primarily focuses on assessing the safety of combining ruxolitinib with CHOP. While each drug's safety is established, the trial aims to evaluate their combined effects. Researchers are closely monitoring for any side effects or reactions to ensure patient safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for lymphoma, like the standard CHOP regimen (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone), work by attacking rapidly dividing cells. But Ruxolitinib adds a new twist by targeting specific signaling pathways, namely the Janus kinase (JAK) pathway, which plays a key role in the growth and survival of cancer cells. Researchers are excited about this combination because Ruxolitinib may enhance the effectiveness of the CHOP regimen by specifically disrupting cancer cell communication, potentially leading to better outcomes for patients. This targeted approach offers a promising new angle in the fight against lymphoma, aiming to improve response rates and reduce side effects.

What evidence suggests that this treatment might be an effective treatment for TFH cell lymphoma?

Research has shown that ruxolitinib alone has limited effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), with patients experiencing disease progression-free survival for about 1.8 months and overall survival for about 5 months. The CHOP treatment, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, is a well-established method for treating certain types of lymphoma. It damages the DNA of cancer cells and stops them from growing. In this trial, participants will receive a combination of ruxolitinib and CHOP to test if it can improve outcomes by blocking proteins that help cancer cells grow. Early findings suggest this combination might be more effective against TFH cell lymphoma, but further research is needed to confirm its benefits. ^{1 2 6 7 8}

Who Is on the Research Team?

Christina Poh

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with untreated nodal T-follicular helper cell lymphoma. Participants should not have had previous treatments for this condition. Specific eligibility criteria are not provided, but typically include factors like age, overall health status, and the stage of the disease.

Inclusion Criteria

Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)

Absolute neutrophil count (ANC) ≥ 1,000/mm^3

Hemoglobin ≥ 8 g/dL

Exclusion Criteria

I have been diagnosed with cirrhosis.

I have had a blood clot in the past 6 months.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment (Part A)

Participants receive ruxolitinib in combination with CHOP chemotherapy for up to 6 cycles

18 weeks

6 visits (in-person)

Maintenance (Part B)

Participants receive ruxolitinib monotherapy for up to 12 cycles

12 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Ruxolitinib
• Vincristine

Trial Overview

The trial is testing the safety and effectiveness of ruxolitinib combined with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating nodal TFH cell lymphoma. Ruxolitinib targets proteins that may help cancer cells grow; CHOP drugs work by damaging DNA or inhibiting cell division.

How Is the Trial Designed?

Group I: Treatment (ruxolitinib, CHOP) Experimental Treatment 16 Interventions

See Detailed Description

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7970687/

Rituximab in combination with cyclophosphamide ...

R-CHOP cures approximately 70% of DLBCL patients. Dose-dense regimens do not show a benefit in response and increase toxicity.

2.

ejcancer.com

ejcancer.com/article/S0959-8049(22)00743-2/pdf

Impact of rituximab on treatment outcomes of patients with ...

Patients are treated with either cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or with the same regimen with additional ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/23615461/

Rituximab plus cyclophosphamide, doxorubicin, vincristine, ...

Findings: 1080 patients were assigned to R-CHOP-21 (n=540) and R-CHOP-14 (n=540). With a median follow-up of 46 months (IQR 35-57), 2-year OS was 82·7% (79·5- ...

4.

researchgate.net

researchgate.net/publication/348901807_Rituximab_in_combination_with_cyclophosphamide_doxorubicin_vincristine_and_prednisone_R-CHOP_in_diffuse_large_B-cell_lymphoma

(PDF) Rituximab in combination with cyclophosphamide ...

R-CHOP cures approximately 70% of DLBCL patients. Dose-dense regimens do not show a benefit in response and increase toxicity.

5.

link.springer.com

link.springer.com/article/10.1186/s13045-020-01011-z

New agents and regimens for diffuse large B cell lymphoma

Ruxolitinib produced a median PFS of 1.8 months and OS of 5 months in r/r DLBCL who were ineligible for, or failed SCT (n = 32) [123]. According ...

6.

link.springer.com

link.springer.com/article/10.1186/s12885-019-6303-z

Ruxolitinib shows activity against Hodgkin lymphoma but not ...

In our study, ruxolitinib showed acceptable efficacy for relapsed/refractory HL patients. However, only one patient achieved CR, and the ...

7.

haematologica.org

haematologica.org/article/view/haematol.2021.280275

Past, present and future therapeutic approaches in nodal ...

Overall, the 3-year PFS was 50% and the 3-year OS was 60%, highlighting better outcomes in the more modern treatment era. Furthermore, using ...

8.

ashpublications.org

ashpublications.org/blood/article/144/18/1887/514805/Current-and-upcoming-treatment-approaches-to

Current and upcoming treatment approaches to common ...

A small phase 2 study evaluated frontline treatment with azacytidine plus CHOP in 20 patients with PTCL, including 17 patients with TFH lymphoma ...