Combination Therapy for Lymphoma

Not currently recruiting at 16 trial locations

Overseen By Annette Hay

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Live vaccines

Disqualifiers: Other malignancies, CNS involvement, HIV, 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: Unknown

Duration: 21 days per cycle, multiple cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests new combinations of treatments for specific types of lymphoma, a kind of blood cancer. The goal is to compare these new treatment options to the standard ones typically used. People with certain types of B-cell lymphoma that have not responded to previous treatments or have recurred may be suitable candidates. Participants should have a lymphoma diagnosis that affects their daily life, such as low energy levels or significant symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the R-DICEP treatment has been under study for some time. Regular safety checks confirm that the combination of rituximab, cyclophosphamide, etoposide, and cisplatin is manageable for most patients, though it can be intense, with some experiencing severe side effects.

For the Ibrutinib plus R-GDP treatment, studies indicate that while this drug combination can be hard on the body, many patients tolerate it. This treatment includes ibrutinib, rituximab, gemcitabine, dexamethasone, and cisplatin, and has undergone various trials with safety evaluations.

The Selinexor plus R-GDP treatment has demonstrated a generally tolerable safety profile. Patients in studies have managed the side effects, and the treatment has shown promise in controlling the disease.

All these treatments have progressed through earlier research stages, indicating some level of safety evaluation. However, side effects can vary, so discussing potential impacts on health with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer innovative approaches to tackling lymphoma. Ibrutinib, for example, is a standout because it blocks Bruton's tyrosine kinase, interrupting signals that encourage lymphoma cell growth — a mechanism different from traditional chemotherapy. Selinexor is another unique treatment, functioning as a selective inhibitor of nuclear export, which traps tumor-suppressing proteins in the cell nucleus to fight cancer cells more effectively. These mechanisms provide new avenues to potentially improve treatment outcomes compared to the standard regimens that rely largely on conventional chemotherapy drugs.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that the R-DICEP treatment, one of the study arms in this trial, can be effective for aggressive non-Hodgkin lymphoma. Studies indicate that this combination helps many patients qualify for stem cell transplants, with nearly half surviving for at least five years. Another arm in this trial, the Ibrutinib plus R-GDP combination, is under investigation for its potential as a promising option for lymphoma that has returned or is difficult to treat, as it combines a targeted drug (Ibrutinib) with chemotherapy. Lastly, the Selinexor with R-GDP arm demonstrated a 67% response rate in patients with relapsed or hard-to-treat B-cell lymphoma, making it a strong option. Researchers are studying these treatments in this trial to compare them with standard care for lymphoma. ^{1 3 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Cyclophosphamide
• Dexamethasone
• Etoposide
• G-CSF
• Gemcitabine
• Ibrutinib
• Mesna
• Rituximab
• Selinexor

Trial Overview The 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.

How Is the Trial Designed?

Group I: Selinexor + R-GDP Experimental Treatment 5 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 Treatment 6 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 Treatment 5 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-GDP Active Control 4 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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union 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 United States 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 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

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Karyopharm Therapeutics Inc

Industry Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

Cisplatin is a widely used cancer treatment but can cause serious dose-dependent toxicities, including nausea, renal insufficiency, and myelosuppression, especially in cases of overdose.

There are currently no specific antidotes for cisplatin overdose, but management strategies include aggressive hydration, monitoring, and supportive therapies, with some experimental treatments showing limited effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

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]

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]

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]

Cisplatin and carboplatin have shown effective responses in treating non-Hodgkin's lymphomas, particularly in cases of primary resistance or relapses, with cisplatin-based combinations prolonging survival in 30-40% of patients.

Effective antiemetic therapies, like ondansetron and granisetron, have reduced the fear of vomiting associated with these treatments, leading to increased use of cisplatin and carboplatin combinations in resistant malignant lymphoproliferative diseases.

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]

In a study of 97 patients with advanced malignant lymphomas resistant to previous chemotherapy, the combination chemotherapy regimens V-PLAT and V-HEX showed limited antitumor activity, with objective response rates of 20% and 8%, respectively.

Despite the higher toxicity associated with V-PLAT, particularly hematologic toxicity, the overall median survival for patients was approximately 6 months, indicating that neither regimen significantly improved outcomes compared to previous treatments with VM-26 or hexamethylmelamine alone.

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]

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]

The DNCE regimen (which includes DXM, NVB, DDP, and Vp-16) shows comparable efficacy to the DICE regimen (DXM, IFO, DDP, and Vp-16) in treating refractory or relapsed aggressive non-Hodgkin lymphoma, with similar response rates but no statistically significant differences.

Patients receiving the DNCE regimen experienced significantly less bone marrow toxicity compared to those on the DICE regimen, making DNCE a safer second-line treatment option.

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 26 patients with refractory or recurrent lymphoma, the combination of cis-platinum, VP-16, and MGBG resulted in a 20% complete remission rate and a 40% partial remission rate among non-Hodgkin's lymphoma patients, indicating some efficacy of this treatment regimen.

The treatment was associated with significant toxicity, including severe side effects like leukopenia, thrombocytopenia, and profound peripheral neuropathy, which led to treatment discontinuation in some cases.

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]

Cis-dichlorodiammineplatinum(II) can cause serious side effects such as nephrotoxicity, gastrointestinal issues (like nausea and vomiting), and myelosuppression, highlighting the need for careful monitoring during treatment.

Other potential side effects include ototoxicity (which can lead to hearing loss), anaphylactic reactions, and peripheral neuropathies, indicating that while the drug may be effective, its safety profile requires close attention.

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6726277/

Emerging therapies for the treatment of relapsed or refractory ... A phase i/ii study is examining the combination of ibrutinib, lenalidomide, and rituximab in patients with non-gcb r/r dlbcl. In 55 evaluable patients, median ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8997053/

Ibrutinib Associated with Rituximab-Platinum Salt-Based ... Ibrutinib associated with Rituximab-Platinum salt-based immunochemotherapy in B-cell lymphomas: results of a Phase 1b-II study of the LYSA group.

3. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)00289-1/fulltext

SOHO State of the Art Updates and Next Questions 12 trial randomized 619 patients with relapsed/refractory aggressive lymphoma to receive GDP (gemcitabine, dexamethasone, and cisplatin) versus ...

4. researchgate.net researchgate.net/publication/383987384_A_randomized_trial_of_ibrutinib_and_R-GDP_prior_to_stem_cell_transplant_in_relapsed_diffuse_large_B-cell_lymphoma

A randomized trial of ibrutinib and R‐GDP prior to stem cell ... An ongoing multi‐arm randomized phase II trial evaluating novel salvage therapies compared with R‐GDP (rituximab, gemcitabine, dexamethasone and cisplatin)

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0037196323000975

Second-line treatment of diffuse large B‐cell lymphoma In the era of immunochemotherapy, approximately 60%-70% of diffuse large B-cell lymphoma (DLBCL) patients achieve remission with first-line rituximab-based ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02436707

Study Details | NCT02436707 | Novel Combination ... All novel treatment options will be compared against the standard treatment for this disease: rituximab plus gemcitabine, dexemthasone, and cisplatin (R-GDP).

7. bloodresearch.or.kr bloodresearch.or.kr/journal/view.html?pn=search&uid=2644&vmd=Full

Ibrutinib combined with gemcitabine-vinorelbine for ... Second- and third-line chemotherapies are rituximab, dexamethasone, cisplatin ... lymphoma (RR-DLBCL) - outcome of ibrutinib + R-GDP. Hematol Oncol 2017;35:88 ...