Only 8 spots left

~8 spots leftby Dec 2025

Combination Therapy for Lymphoma

Recruiting in Palo Alto (17 mi)

+15 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Canadian Cancer Trials Group

Must not be taking: Live vaccines

Disqualifiers: Other malignancies, CNS involvement, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination therapy for lymphoma?

Research shows that combinations including drugs like dexamethasone, etoposide, and cisplatin have been effective in treating aggressive non-Hodgkin's lymphoma, with some patients achieving complete responses. Additionally, regimens with rituximab have shown excellent results for certain types of lymphoma.¹ ² ³ ⁴ ⁵

Is the combination therapy for lymphoma generally safe in humans?

The combination therapy involving drugs like Cisplatin and Etoposide has shown moderate to severe side effects, including nausea, vomiting, kidney issues, nerve damage, and blood cell problems. Cisplatin, in particular, can cause serious side effects like kidney damage, hearing loss, and nerve damage, and requires careful monitoring during treatment.⁶ ⁷ ⁸ ⁹ ¹⁰

What makes the combination therapy for lymphoma unique?

This combination therapy for lymphoma is unique because it includes a mix of drugs like cisplatin, cyclophosphamide, and ibrutinib, which are not typically used together in standard treatments. It targets lymphoma with a multi-faceted approach, potentially offering benefits for patients who have not responded to conventional therapies.² ³ ¹¹ ¹² ¹³

Research Team

John Kuruvilla

Principal Investigator

Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada

Michael Crump

Principal Investigator

Univ. Health Network-OCI/Princess Margaret Hospital, Toronto ON Canada

Eligibility Criteria

This trial is for people over 16 and under 65 with aggressive B-cell lymphoma that's come back or hasn't responded to treatment. They should have had only one prior therapy (up to three if the cancer transformed from a low-grade type). Participants need measurable disease, good organ function, and an ECOG status of 0-2, indicating they can handle intensive chemotherapy. Women must use birth control or be post-menopausal.

Inclusion Criteria

Clinically and/or radiologically measurable disease

Laboratory Requirements within specified ranges

Life expectancy > 90 days

See 9 more

Exclusion Criteria

I have had cancer before, but it fits the exceptions listed.

I do not have HIV, active Hepatitis B or C, or any uncontrolled infections.

I have not received any live vaccines in the last 4 weeks.

See 5 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive novel combination therapies compared against standard treatment (R-GDP) for relapsed and refractory aggressive B-cell lymphoma

21 days per cycle, multiple cycles

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety, tolerability, and effectiveness after treatment

2 years

Ongoing monitoring with annual reporting

Safety Run-in

Initial safety assessment for the first six patients assigned to ibrutinib plus R-GDP

Initial phase within treatment

Treatment Details

Interventions

Cisplatin (Alkylating agents)
Cyclophosphamide (Chemotherapy)
Dexamethasone (Corticosteroid)
Etoposide (Anti-tumor antibiotic)
G-CSF (Other)
Gemcitabine (Anti-metabolites)
Ibrutinib (Kinase Inhibitor)
Mesna (Other)
Rituximab (Monoclonal Antibodies)
Selinexor (Other)

Trial OverviewThe study tests new combinations of drugs against standard treatments for relapsed/refractory aggressive B-cell lymphoma. Drugs include Cyclophosphamide, Rituximab, Etoposide, Cisplatin, Dexamethasone, Selinexor, Gemcitabine, Mesna, Ibrutinib & G-CSF. The goal is to see how these combinations affect the disease.

Participant Groups

4Treatment groups

Experimental Treatment

Active Control

Group I: Selinexor + R-GDPExperimental Treatment5 Interventions

Selinexor - 40mg PO, D1, D3, D8 Rituximab - 375 mg/m2 IV, 1.5 - 6 hours D1 (prior to cisplatin); Gemcitabine - 1000 mg/m2, IV 30 min D1, D8; Dexamethasone - 40 mg daily PO D1 - D4; Cisplatin - 75 mg/m2 IV, 1 hour D1;

Group II: R-DICEP (ACCRUAL COMPLETE)Experimental Treatment6 Interventions

Rituximab 375 mg/m2 IV 1.5-6hrs Day 1 and Day 5 prior to Cisplatin Mesna 1.75 g/m2 IV 24 hour Cycle 1, Day 2, Day 3 and Day 4 Cyclophosphamide, 1.75 g/m2 IV 2 hours, Day 2, Day 3 and Day 4 Etoposide 350 mg/m2 IV 2 hours, Day 2, Day 3 and Day 4 Cisplatin 35 mg/m2 IV, 2 hours, Day 2, Day 3 and Day 4 G-CSF 300 mcg (\<60kg); 480 mcg (60-90kg); 600 mcg (\>90kg); SC, Daily, starting Day 15 until apheresis completed.

Group III: Ibrutinib plus R-GDP (ACCRUAL COMPLETE)Experimental Treatment5 Interventions

Ibrutinib 560 mg PO -- D1 - D21 Rituximab 375 mg/m2 IV 1.5 - 6 hours D1 (prior to cisplatin) Gemcitabine 1000 mg/m2 IV 30 min D1, D8 Dexamethasone 40 mg daily PO -- D1 - D4 Cisplatin 75 mg/m2 IV 1 hour D1

Group IV: R-GDPActive Control4 Interventions

Rituximab - 375 mg/m2 IV, 1.5 - 6 hours D1 (prior to cisplatin); Gemcitabine - 1000 mg/m2, IV 30 min D1, D8; Dexamethasone - 40 mg daily PO D1 - D4; Cisplatin - 75 mg/m2 IV, 1 hour D1;

Cisplatin is already approved in Canada, Japan for the following indications:

Approved in Canada as Platinol for:

Testicular cancer
Ovarian cancer
Cervical cancer
Bladder cancer
Head and neck cancer
Esophageal cancer
Lung cancer
Mesothelioma
Brain tumors
Neuroblastoma

Approved in Japan as Platinol for:

Testicular cancer
Ovarian cancer
Cervical cancer
Bladder cancer
Head and neck cancer
Esophageal cancer
Lung cancer
Mesothelioma
Brain tumors
Neuroblastoma

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:

QEII Health Sciences CentreHalifax, Canada

CancerCare ManitobaWinnipeg, Canada

Allan Blair Cancer CentreRegina, Canada

Juravinski Cancer Centre at Hamilton Health SciencesHamilton, Canada

More Trial Locations

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Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Patients Recruited

70,300+

Janssen, LP

Industry Sponsor

Trials

169

Patients Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[DNCE regimen for treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma].Liu, XM., Wang, HQ., Zhang, HL., et al.[2018]

In a study of 30 patients with refractory or relapsing non-Hodgkin's lymphoma, the DVIP treatment led to a 33% complete response rate and a 30% partial response rate, with responses lasting from 2.5 to over 24 months.

While DVIP treatment caused significant myelosuppression, it was considered safe as there were no drug-related deaths, indicating it is an effective salvage therapy for aggressive forms of NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin.Haim, N., Rosenblatt, E., Wollner, M., et al.[2019]

New chemotherapy combinations, such as IMVP-16 and MIME, have shown promising results in lymphoma patients, achieving overall response rates of 60% and complete response rates of 25%.

Long-term follow-up of the MIME regimen indicates a 25% cure rate for intermediate-grade lymphoma patients who achieve a complete response, highlighting its potential effectiveness as a salvage treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with salvage regimens at M.D. Anderson Hospital.Cabanillas, F.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma].Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

The ESHAOx regimen, which replaces cisplatin with oxaliplatin, showed a 63% overall response rate in 27 patients with refractory or relapsed aggressive non-Hodgkin's lymphoma, indicating its potential effectiveness as a treatment option.

While the treatment resulted in significant hematologic toxicities like neutropenia (56%) and thrombocytopenia (35%), it did not cause severe renal or neurotoxicity, suggesting a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter phase II trial of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin for patients with primary refractory/relapsed aggressive non-Hodgkin's lymphoma.Sym, SJ., Lee, DH., Kang, HJ., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, VP-16-213 and MGBG (methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study.Dabich, L., Liepman, MK.[2019]

Carboplatin, a platinum analogue of cisplatin, shows comparable antitumor activity against various cancers while significantly reducing renal and neurotoxic side effects, making it a safer alternative.

Preliminary studies on iproplatin indicate it may also have reduced renal and neurologic toxicity similar to carboplatin, with efficacy comparable to cisplatin, suggesting it could be another promising option in chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and II agents in cancer therapy: two cisplatin analogues and high-dose cisplatin in hypertonic saline or with thiosulfate protection.Fuks, JZ., Wadler, S., Wiernik, PH.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin overdose: toxicities and management.Tsang, RY., Al-Fayea, T., Au, HJ.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic effects of cis-dichlorodiammineplatinum(II) in man.Von Hoff, DD., Schilsky, R., Reichert, CM., et al.[2022]

A 60-year-old woman with squamous lung carcinoma experienced paroxysmal supraventricular tachycardia during treatment with cisplatin and etoposide, highlighting a potential cardiac side effect of cisplatin.

The case suggests that caution should be exercised when administering cisplatin to patients with existing cardiac conditions or those who have received other cardiotoxic cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paroxysmal supraventricular tachycardia during treatment with cisplatin and etoposide combination.Fassio, T., Canobbio, L., Gasparini, G., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cisplatin and carboplatin in the treatment of malignant lymphoma and multiple myeloma].Adam, Z., Mayer, J., Hájek, R.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative trial of two teniposide-based combination chemotherapy regimens for the treatment of advanced malignant lymphomas.O'Connell, MJ., Anderson, J., Merrill, JM., et al.[2013]

The DVIP regimen (dexamethasone, etoposide, ifosfamide, and cisplatin) demonstrated a significant response rate in patients with aggressive non-Hodgkin's lymphoma, achieving a complete response in 32% of the 56 patients studied, with a median survival of 30 months for those who achieved complete response.

Age and prior treatment response were identified as key predictors of treatment success, with younger patients and those who responded well to previous therapies having better outcomes, while myelosuppression was the main side effect observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone, etoposide, ifosfamide, and cisplatin as second-line therapy in patients with aggressive non-Hodgkin's lymphoma.Haim, N., Ben-Shahar, M., Faraggi, D., et al.[2019]

References

1.Chinapubmed.ncbi.nlm.nih.gov

[DNCE regimen for treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma]. [2018]

2.Germanypubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. [2019]

3.Englandpubmed.ncbi.nlm.nih.gov

Experience with salvage regimens at M.D. Anderson Hospital. [2020]

4.Japanpubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. [2015]

5.Germanypubmed.ncbi.nlm.nih.gov

A multicenter phase II trial of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin for patients with primary refractory/relapsed aggressive non-Hodgkin's lymphoma. [2018]

6.United Statespubmed.ncbi.nlm.nih.gov

Cisplatin, VP-16-213 and MGBG (methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study. [2019]

7.Englandpubmed.ncbi.nlm.nih.gov

Phase I and II agents in cancer therapy: two cisplatin analogues and high-dose cisplatin in hypertonic saline or with thiosulfate protection. [2019]

8.New Zealandpubmed.ncbi.nlm.nih.gov

Cisplatin overdose: toxicities and management. [2022]

9.United Statespubmed.ncbi.nlm.nih.gov

Toxic effects of cis-dichlorodiammineplatinum(II) in man. [2022]

10.Switzerlandpubmed.ncbi.nlm.nih.gov

Paroxysmal supraventricular tachycardia during treatment with cisplatin and etoposide combination. [2018]

11.Czech Republicpubmed.ncbi.nlm.nih.gov

[Cisplatin and carboplatin in the treatment of malignant lymphoma and multiple myeloma]. [2013]