Ascorbic Acid + Chemotherapy for Lymphoma

Recruiting at 6 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Platinum-based regimens

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Active infection, Heart failure, 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

Duration: 12 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients on ibrutinib or corticosteroids may continue therapy until the new regimen starts, at the investigator's discretion. It's best to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the drug combination including Ascorbic Acid and Rituximab for treating lymphoma?

Research shows that adding rituximab to chemotherapy regimens for lymphoma, such as R-CHOP, improves treatment outcomes and survival rates. Rituximab has been effective in enhancing the response to chemotherapy in various types of lymphoma, suggesting potential benefits when combined with other drugs like Ascorbic Acid. ^{1 2 3 4 5}

Is the combination of ascorbic acid and chemotherapy drugs like carboplatin and cisplatin safe for humans?

Research shows that carboplatin and cisplatin, when used together, can have manageable side effects like low blood cell counts, nausea, and vomiting, but they are generally considered safe with careful monitoring. Carboplatin is noted for having fewer kidney-related side effects compared to cisplatin, making it a safer option in some cases. ^{6 7 8 9 10}

What makes the Ascorbic Acid + Chemotherapy treatment for lymphoma unique?

This treatment combines ascorbic acid (vitamin C) with a mix of chemotherapy drugs, including rituximab, which has shown improved response rates and survival in lymphoma patients. The unique aspect is the addition of ascorbic acid, which may enhance the effectiveness of chemotherapy, although its precise role in lymphoma treatment is still being studied. ^{1 2 11 12 13}

What is the purpose of this trial?

This trial tests if adding high doses of vitamin C to standard chemotherapy can better treat certain cancers that have returned or are resistant to treatment. The goal is to see if vitamin C makes the chemotherapy more effective at killing cancer cells. The study focuses on patients with specific types of lymphoma, CCUS, and CMML. High-dose intravenous vitamin C (IVC) has been explored for its potential to enhance the effectiveness of cancer chemotherapy, with some clinical evidence suggesting benefits, though rigorous data are lacking.

Research Team

Thomas E. Witzig, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults with recurrent or refractory lymphoma, including various subtypes like Diffuse Large B-Cell Lymphoma, who haven't responded to therapy within 6 months or have relapsed after a response lasting more than 6 months. Participants must be in good physical condition (ECOG PS 0-2), able to return for follow-up, and have measurable disease. They should not be pregnant/nursing and must agree to use contraception.

Inclusion Criteria

Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)

My white blood cell count is healthy.

Patients must meet specific laboratory criteria to be enrolled

Exclusion Criteria

Receiving any other investigational agent which would be considered as a treatment for the lymphoma

I have been diagnosed with a blood cancer.

I have active brain lymphoma or cancer cells in my spinal fluid needing specific treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ascorbic acid and combination chemotherapy. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

12 weeks

Multiple visits for IV administration on days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months, then every 6 months after progressive disease for up to 2 years.

Up to 2 years

Regular follow-up visits every 3 to 6 months

Extension

Participants with stable disease after 12 cycles may continue decitabine with or without ascorbic acid as long as clinically appropriate.

As long as clinically appropriate

Treatment Details

Interventions

• Ascorbic Acid
• Carboplatin
• Cisplatin
• Cytarabine
• Dexamethasone
• Etoposide
• Gemcitabine Hydrochloride
• Ifosfamide
• Rituximab

Trial Overview The trial is testing the effectiveness of ascorbic acid (vitamin C) combined with chemotherapy drugs such as Ifosfamide, Carboplatin, Etoposide, Rituximab and others against lymphomas that are difficult to treat. The goal is to see if vitamin C can make cancer cells more vulnerable to chemo.

Participant Groups

Group I: Arm D (ascorbic acid) Experimental Treatment 8 Interventions

Patients receive ascorbic acid IV TIW. Treatments repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PICC or portacath placement prior to starting treatment, blood sample collection, bone marrow aspiration and biopsy throughout study.

Group II: Arm C (ascorbic acid and combination chemotherapy) Experimental Treatment 19 Interventions

Patients receive ascorbic acid IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Patients also receive ifosfamide, carboplatin, and etoposide IV or PO, or cisplatin, cytarabine, and dexamethasone IV or PO, or gemcitabine hydrochloride, dexamethasone, and cisplatin IV or PO, or gemcitabine hydrochloride and oxaliplatin IV or PO, or oxaliplatin, cytarabine, and dexamethasone IV or PO according to standard regimen schedule. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve MR or SD after 2 cycles may switch to an alternative chemotherapy regimen. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, ECHO, PET/CT or MRI throughout study.

Group III: Arm A (ascorbic acid, combination chemotherapy) Experimental Treatment 18 Interventions

Patients receive ascorbic acid IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19, and rituximab intravenously IV, ifosfamide IV, carboplatin IV and etoposide IV on days 1-3. Patients who achieve MR or SD after 2 cycles may receive rituximab IV or PO, cisplatin IV or PO, cytarabine IV or PO, and dexamethasone IV or PO. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, ECHO, PET/CT or MRI throughout study.

Group IV: ARM E (ascorbic acid, decitabine) Experimental Treatment 7 Interventions

Patients receive ascorbic acid IV on days 1, 3 and 5 and decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 12 cycles may continue decitabine with or without ascorbic acid as long as clinically appropriate. Patients may also take vitamin C PO on days 6-28. Patients undergo PICC or portacath placement prior to starting treatment, blood sample collection, bone marrow aspiration and biopsy throughout study.

Group V: Arm B (placebo, combination chemotherapy) Active Control 18 Interventions

Patients receive placebo (normal saline) IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19, and rituximab intravenously IV, ifosfamide IV, carboplatin IV and etoposide IV on days 1-3. Patients who achieve MR or SD after 2 cycles may receive rituximab IV or PO, cisplatin IV or PO, cytarabine IV or PO, and dexamethasone IV or PO. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, ECHO, PET/CT or MRI throughout study.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[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]

In a study of 50 HIV-positive patients with high-risk diffuse large B-cell lymphoma (DLBCL), 68% achieved complete remission, indicating a favorable outcome for this patient group.

While treatment intensification with CODOX-M/IVAC ± R resulted in more infections and non-hematological toxicities, it did not show any significant advantage over the standard R-CHOP regimen in terms of overall survival or progression-free survival, with both groups having similar outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective, multi-center analysis of treatment intensification for human immunodeficiency virus-positive patients with high-risk diffuse large B-cell lymphoma. Kassam, S., Bower, M., Lee, SM., et al.[2019]

The addition of rituximab to standard chemotherapy regimens like CHOP and ACVBP significantly improves treatment outcomes for lymphoma patients, allowing for fewer cycles of treatment without compromising efficacy.

Using positron emission tomography (PET) scans early in treatment can help predict long-term outcomes, enabling personalized treatment plans based on individual patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current approaches to the treatment of non-Hodgkin's lymphoma. Gisselbrecht, C.[2021]

In a study of 41 patients with advanced cervical cancer receiving carboplatin, the overall response rate was 15%, indicating modest efficacy with two complete and four partial responses.

Carboplatin had a more favorable toxicity profile compared to cisplatin, with major side effects including nausea (48%), anemia (47%), and leukopenia (38%), suggesting it may be a safer option for further exploration in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Weiss, GR., Green, S., Hannigan, EV., et al.[2019]

In a phase II study involving 56 patients with small cell lung carcinoma, carboplatin demonstrated significant efficacy, with a 41% overall response rate and 9% achieving complete remission, particularly in previously untreated patients where the response rate was 60%.

Carboplatin showed a favorable safety profile, with no nephrotoxicity and manageable side effects; while some patients experienced myelosuppression, severe complications were rare, suggesting it may be a better-tolerated alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer. Smith, IE., Harland, SJ., Robinson, BA., et al.[2013]

In a Phase I trial involving 18 patients with advanced non-small cell lung cancer (NSCLC), the combination of carboplatin and cisplatin was found to have a manageable toxicity profile, with thrombocytopenia being the main dose-limiting effect and a maximum tolerated dose of 350 mg/m2 for carboplatin.

In a subsequent Phase II trial with 13 patients, using a safer carboplatin dose of 300 mg/m2, 38.5% of patients showed a partial response to the treatment, indicating that this combination chemotherapy may be effective for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. Nakanishi, R., Kume, T., Mitsudomi, T., et al.[2019]

In a phase I trial involving 26 adult patients with solid tumors, carboplatin was administered safely at doses of 40-125 mg/m2, showing a manageable safety profile with dose-related side effects like thrombocytopenia and neutropenia.

Although no patients achieved a complete or partial response, there were indications of antitumor effects in two patients, suggesting that carboplatin could be a promising candidate for further testing in phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin given on a five-day intravenous schedule. Rozencweig, M., Nicaise, C., Beer, M., et al.[2022]

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]

In a study of 23 patients with aggressive B-cell non-Hodgkin lymphoma, the combination of rituximab with CODOX-M/IVAC showed promising efficacy, with 83% of low-risk and 71% of high-risk patients achieving complete remission after treatment.

The safety profile was acceptable, with no treatment-related deaths and manageable toxicity, including only two cases of grade 3 neutropenia, suggesting that this treatment combination is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. Mohamedbhai, SG., Sibson, K., Marafioti, T., et al.[2015]

In a study involving 25 patients with advanced Hodgkin's disease and non-Hodgkin's lymphoma, cis-dichlorodiammineplatinum(II) showed limited efficacy, resulting in one complete response and two partial responses, indicating it may have some therapeutic potential.

The treatment was associated with significant myelosuppression, particularly leukopenia and thrombocytopenia, which were more severe than in previous studies, likely due to the patients' extensive prior treatments and the presence of tumor-bearing marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. Rossof, AH., Coltman, CA., Jones, SE., et al.[2013]

In a phase II trial involving 51 patients with relapsed lymphoma, the combination of gemcitabine, carboplatin, dexamethasone, and rituximab (GCDR) demonstrated a 67% overall response rate and a 31% complete response rate, indicating its efficacy as a salvage treatment.

The regimen was found to be safe, with low rates of severe adverse events (only 2.5% experienced febrile neutropenia) and no treatment-related deaths, while also effectively mobilizing stem cells for potential transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Gopal, AK., Press, OW., Shustov, AR., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? [2022]

2. England pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. [2022]

3. Japan 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]. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

A retrospective, multi-center analysis of treatment intensification for human immunodeficiency virus-positive patients with high-risk diffuse large B-cell lymphoma. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Current approaches to the treatment of non-Hodgkin's lymphoma. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin given on a five-day intravenous schedule. [2022]

10. England 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. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. [2013]

13. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. [2022]