Chemo + Radiation for Nasal NK Cell Lymphoma

Recruiting at 1 trial location

Overseen By Bouthaina S. Dabaja

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Hepatitis B, Hepatitis C, HIV, cardiovascular disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining chemotherapy and radiation therapy can control Stage 1 and Stage 2 NK cell lymphoma, a cancer in the nasal area. The study also examines the safety of using these treatments together. Individuals with newly diagnosed Stage 1 or 2 nasal NK cell lymphoma who believe they can manage their blood and liver health might consider participating. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have pre-existing cardiovascular disease requiring ongoing treatment, you may not be eligible to participate.

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

Previous studies have shown that radiation therapy is generally safe for patients with early-stage NK/T-cell lymphoma. Patients tolerated low-dose radiation (less than 50 Gy) well, with few serious side effects reported. Regarding the chemotherapy drugs used:

Carboplatin and etoposide phosphate have treated various cancers, and their safety is well-established. Most patients handle these drugs without major problems, though some might experience side effects like nausea or tiredness.

Ifosfamide, another chemotherapy drug included in the treatment, has been used in similar situations and is generally safe when monitored carefully. However, it may cause more noticeable side effects, such as changes in blood cell counts or kidney function.

These treatments have FDA approval for other conditions, indicating they are considered reasonably safe. However, using them together with radiation therapy in this specific way is still under study, so monitoring for any unique side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for nasal NK cell lymphoma because it combines chemotherapy with radiation therapy in a unique way. Unlike standard treatments that often use chemotherapy or radiation alone, this approach integrates both, potentially enhancing their effectiveness. The specific chemotherapy regimen, known as DeVIC, includes carboplatin, etoposide, ifosfamide, and dexamethasone, which are administered in a way that complements the radiation therapy. This combination might offer a more powerful attack on cancer cells, leading to better outcomes for patients.

What evidence suggests that this combination of chemotherapy and radiation therapy could be effective for NK cell lymphoma?

Research has shown that using both radiation and chemotherapy effectively treats early-stage NK cell lymphoma. In this trial, participants will receive a combination of radiation therapy and chemotherapy drugs, including carboplatin, etoposide, and ifosfamide. Radiation therapy alone has succeeded, with many patients responding well and living longer. When combined with these chemotherapy drugs, the treatments work together to better target and destroy cancer cells. Studies have demonstrated that this combination can lead to complete remission in many patients. The overall results of this combined approach have been promising, with many patients experiencing significant and lasting improvements. ^{6 7 8 9 10}

Who Is on the Research Team?

Bouthaina S. Dabaja

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed stage I or II nasal NK cell lymphoma. Participants need normal blood counts, kidney and liver function, heart efficiency (ejection fraction ≥50%), and must not be pregnant or breastfeeding. They should agree to use contraception if of childbearing potential and have no active infections like Hepatitis B/C, HIV, severe heart conditions, or psychiatric issues that affect compliance.

Inclusion Criteria

Patients are required to have a serum creatinine </= 2.0 mg/dL (value obtained within two weeks before protocol entry)

Left ventricular ejection fraction must be evaluated by nuclear medicine scan or echocardiography and measure >/= 50%

I have been diagnosed with early-stage nasal NK cell lymphoma.

Exclusion Criteria

I do not have any active infections needing treatment.

I have a serious heart condition that needs ongoing treatment.

I've had radiation before where my cancer is now, and can't have more without risking harm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive radiation therapy 5 days a week for 28 to 30 treatments

6 weeks

Weekly visits for physical exams and blood tests

Chemotherapy

Participants receive up to 3 cycles of chemotherapy, each cycle lasting 21 days

9 weeks

Visits on or before Day 1, Day 15 of Cycle 2, and Day 15 of Cycle 3 for blood tests and possible EKG

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for the 1st year, every 4 months during the 2nd year, every 6 months during the 3rd-5th years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Dexamethasone
• Etoposide phosphate
• Ifosfamide
• Mesna
• Radiation Therapy

Trial Overview The study tests the effectiveness of combining radiation therapy with chemotherapy drugs Etoposide phosphate, Ifosfamide, Carboplatin, Dexamethasone, and Mesna in controlling early-stage nasal NK cell lymphoma. The safety of this concurrent treatment approach is also being evaluated.

How Is the Trial Designed?

Group I: Chemotherapy + Radiation Therapy Experimental Treatment 6 Interventions

Radiation therapy delivered for a total dose of 50.4 to 54 Gy over 28 to 30 treatments. Within seven days of starting radiotherapy, the first cycle of chemotherapy started and repeated every 3 weeks for a total of 3 cycles. DeVIC on day 1 of every cycle. Dexamethasone 40 mg by vein Days 1-3, Etoposide 67 mg/m2 by vein on Days 1-3, Ifosfamide 1 g/m2 by vein on Days 1-3, Mesna 0.4 g/m2 by vein on Days 1-3 with Ifosfamide, Mesna 0.6 g/m2 by vein over 24 hours daily on Days 1-3 via ambulatory pump, Carboplatin 200 mg/m2 by vein on Day 1. Cycles repeated every 21 days.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a phase III trial involving 200 patients with stage III non-small cell lung cancer, the chemotherapy regimen of etoposide and cisplatin (EP) showed a significantly higher 3-year overall survival rate compared to carboplatin and paclitaxel (PC), with a difference of 15% (P = 0.024).

While EP demonstrated better overall survival, it was associated with a higher incidence of severe esophagitis (20% vs. 6.3% for PC), whereas PC had a higher rate of radiation pneumonitis (33.3% vs. 18.9% for EP), indicating a trade-off in safety profiles between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Liang, J., Bi, N., Wu, S., et al.[2020]

In a study of 57 patients with nasal type extranodal NK/T-cell lymphoma, combining chemotherapy with radiotherapy resulted in a significant improvement in long-term disease-free survival rates compared to chemotherapy alone, especially after 3 and 5 years of follow-up.

The overall effective rates after treatment were similar for both groups (91.2% for the combined treatment and 87.0% for chemotherapy alone), but the long-term survival benefits highlight the importance of incorporating radiotherapy into treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Curative effect of nasal type extranodal NK/T-cell lymphoma by sequential chemotherapy combined radiotherapy compared with chemotherapy]. Wang, C., Bai, H., Xi, R., et al.[2014]

In a phase II trial involving 67 patients with limited small-cell lung cancer, the combination of cisplatin, ifosfamide, and oral etoposide (PIEo) with accelerated hyperfractionated thoracic radiation resulted in a high overall response rate of 78%, with a median overall survival of 23.7 months.

While PIEo showed similar survival rates to conventional treatments, it was associated with significant acute toxicities, including severe granulocytopenia in 55% of patients and esophagitis in 43%, indicating a need for careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, ifosfamide, oral etoposide, and concurrent accelerated hyperfractionated thoracic radiation for patients with limited small-cell lung carcinoma: results of radiation therapy oncology group trial 93-12. Glisson, B., Scott, C., Komaki, R., et al.[2018]

Radiotherapy is the primary treatment for early-stage nasal NK/T-cell lymphoma, showing a much higher complete response (CR) rate of 74.6% compared to only 20.8% for chemotherapy.

The study found that adding chemotherapy to radiotherapy does not significantly improve overall survival or disease-free survival rates, indicating that radiotherapy alone is effective for treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prognostic factors and treatment outcome in early stage nasal NK/T cell lymphoma]. Yao, B., Li, YX., Fang, H., et al.[2010]

In a study of 43 patients with stage I/II extranodal NK/T-cell lymphoma, both sequential chemotherapy followed by radiotherapy (SCRT) and concurrent chemoradiotherapy (CCRT) showed similar 3-year progression-free survival (56% for SCRT vs. 41% for CCRT) and overall survival rates (75% for SCRT vs. 59% for CCRT).

Patients with tumors confined to the nasal cavity and those aged 60 years or younger had better survival outcomes, indicating that tumor location and patient age are important factors in prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in patients with stage I/II extranodal natural killer/T-cell lymphoma, nasal type. Lee, J., Kim, CY., Park, YJ., et al.[2021]

In a phase 2 trial involving 74 patients with intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, the addition of chidamide to intensity-modulated radiation therapy (IMRT) and gemcitabine, dexamethasone, and cisplatin (GDP) resulted in similar efficacy outcomes compared to IMRT + GDP alone, with objective response rates of 86.5% versus 78.4%.

Both treatment groups experienced comparable safety profiles, with the main adverse effects being hematological toxicities and mucositis, indicating that chidamide can be safely added without increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Chemoradiation With or Without Chidamide (Tucidinostat) in Patients With Intermediate- and High-Risk Early-Stage Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma: A Randomized Phase 2 Study in China. Chai, Y., Chen, B., Qi, F., et al.[2022]

In a study of 79 patients with early stage nasal NK/T-cell lymphoma, the overall complete response rate was 68.4%, but the long-term outcomes were poor, with only 35.5% disease-free survival and 37.9% overall survival at 5 years.

Adding anthracycline-containing chemotherapy to radiation therapy did not improve survival rates compared to radiation alone, indicating that radiation therapy remains the primary treatment for this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early stage nasal NK/T-cell lymphoma: clinical outcome, prognostic factors, and the effect of treatment modality. Cheung, MM., Chan, JK., Lau, WH., et al.[2022]

In a phase II trial involving 30 patients with early-stage nasal NK/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) resulted in a 100% response rate, with 73.3% achieving complete responses, indicating high efficacy of this treatment approach.

The treatment was well-tolerated, with only one patient experiencing significant nausea and a notable incidence of grade 4 neutropenia in 12 patients, while the estimated 3-year progression-free survival rate was 85.19%, suggesting a promising long-term outcome for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. Kim, SJ., Kim, K., Kim, BS., et al.[2022]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

The pilot study involving 26 patients with poor-risk Stage III non-small-cell lung carcinoma (NSCLC) showed that the combination of carboplatin, etoposide, and thoracic radiation was well tolerated, with 87% of patients completing the planned radiation treatment.

The treatment resulted in an impressive overall response rate of 87%, with 17% achieving a complete response and a median survival of 12 months, indicating promising efficacy for this regimen in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent carboplatin, etoposide and thoracic radiation for poor-risk stage III non-small-cell lung carcinoma: a pilot study. Lau, DH., Ryu, JK., Gandara, DR., et al.[2019]

In a study of 43 patients with inoperable non-small cell lung cancer (NSCLC), the combination of carboplatin, ifosfamide, and etoposide resulted in a 40% objective response rate, indicating potential efficacy for this treatment regimen.

The treatment was generally well-tolerated, with myelosuppression being the main dose-limiting side effect, while serious issues like nephrotoxicity and neurotoxicity were not observed, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-finding studies with carboplatin, ifosfamide, etoposide, and mesna in non-small cell lung cancer. van Zandwijk, N., ten Bokkel Huinink, WW., Wanders, J., et al.[2018]

In a study of 42 patients with early-stage nasal NK/T-cell lymphoma, high-dose intensity-modulated radiotherapy (IMRT) demonstrated excellent treatment outcomes, with a 2-year locoregional control rate of 93% and overall survival rate of 78%.

The treatment was associated with mild toxicity, as no severe (Grade 4 or 5) acute or late side effects were reported, and the radiation dose to critical structures like the parotid glands was effectively limited to under 20 Gy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mild toxicity and favorable prognosis of high-dose and extended involved-field intensity-modulated radiotherapy for patients with early-stage nasal NK/T-cell lymphoma. Wang, H., Li, YX., Wang, WH., et al.[2022]

In a study of 13 patients with localized NK/T lymphoma, the concurrent chemoradiotherapy (CCRT) using the ESHAP regimen resulted in a high complete remission rate of 92%, demonstrating its efficacy in treating this type of cancer.

Despite the high efficacy, the treatment was associated with significant toxicities, including grade 3-4 hematological toxicity in 92% of patients and mucositis in 46%, highlighting the need for careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Etoposide, Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type. Michot, JM., Mazeron, R., Danu, A., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3916130/

Impact of dexamethasone, etoposide, ifosfamide and ... The reported 5-year overall survival rate for patients with localized nasal NKTCL treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone ( ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/cnr2.1552

Treatment outcomes of T and natural‐killer/T‐cell ... The median PFS and OS for all patients was 4.4 months (95% confidence interval [CI], 2.7–6.0) and 16 months (95% CI, 8.3–45.4) respectively.

3. ashpublications.org ashpublications.org/blood/article/131/23/2528/36945/Advances-in-the-treatment-of-extranodal-NK-T-cell

Advances in the treatment of extranodal NK/T-cell lymphoma ... Ten of 11 patients who received cell therapy achieved disease-free survival for more than 2 years. The results of these studies demonstrated that immunotherapy ...

4. nature.com nature.com/articles/s41375-025-02527-4

Improved prognosis of advanced-stage extranodal NK/T- ... 3: Survival curves of advanced-stage extranodal NK/T-cell lymphoma. ... A The 1-year and 2-year overall survival (OS) of all patients was 53.7% ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JOP.18.00719

Management of NK/T-Cell Lymphoma, Nasal Type Advances in treatment and understanding of the genetic landscape of this disease offer hope for improved treatment outcomes. ... carboplatin (RT- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6476925/

Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type Ifosfamide and carboplatin were chosen because they are not affected by multidrug resistance genes 1, which is frequently expressed in the NNKTL ...

7. ashpublications.org ashpublications.org/blood/article/121/25/4997/125555/How-I-treat-NK-T-cell-lymphomas

How I treat NK/T-cell lymphomas | Blood - ASH Publications Current data indicate that localized nonnasal lymphomas might not fare as well as nasal lymphomas. Nonnasal lymphomas of any stage therefore should be ...

8. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00213-6/fulltext

Early-Stage Extranodal NK/T-Cell Lymphoma, Nasal Type Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT).

9. thelancet.com thelancet.com/journals/lanwpc/article/PIIS2666-6065(25)00087-2/fulltext

Extranodal NK/T-cell lymphoma: an update of ... We did not detect any significant difference in mutation rates between nasal and extranasal ENKTL based on published studies with available data ...

10. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01293-5

How we treat NK/T-cell lymphomas Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations.