Ascorbic Acid + Chemotherapy for Lymphoma
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Breakthrough Therapy
Trial Summary
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.
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.
12345Is 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.
678910What 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.
12111213Eligibility 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
+17 more
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.
+12 more
Trial 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
Participant Groups
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.
5Treatment groups
Experimental Treatment
Active Control
Group I: Arm D (ascorbic acid)Experimental Treatment8 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 Treatment19 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 Treatment18 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 Treatment7 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 Control18 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic Health Systems-MankatoMankato, MN
Mayo Clinic Health System-Eau Claire ClinicEau Claire, WI
Mayo Clinic Health System-Franciscan HealthcareLa Crosse, WI
University of Iowa/Holden Comprehensive Cancer CenterIowa City, IA
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? [2022]Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard of treatment for chemosensitive relapses in diffuse large B-cell lymphoma. The addition of rituximab to chemotherapy has improved the response rate and failure-free survival after first-line treatment and relapses. Fewer relapses are expected, although there is no consensus on the best salvage regimen. The intergroup Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) set the limits for this standard of treatment after first comparing 2 salvage regimens: rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) and rituximab, dexamethasone, aracytine, and cisplatin (R-DHAP). There was no difference in response rates or survivals between these salvage regimens. Several factors affected survival: prior treatment with rituximab, early relapse (
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]CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin-methatrexate/ifusamide, etoposide, cytarabine) chemotherapy is commonly used to treat Burkitt lymphoma and in the HIV-negative population. Rituximab is often added with suggested survival benefits. Concerns over increased toxicity in an already immunocompromized population have prevented its routine addition in people living with HIV (PLWH). This study evaluated the effect on treatment-related toxicity and efficacy of adding rituximab to CODOX-M/IVAC chemotherapy in PLWH.
[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. [2015]Excellent results were reported for dose-dense and dose-intense weekly combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide and additional ara-C) (CHOEA-7) and with rituximab (RCHOEA-7), for patients with CD 20-positive non-Hodgkin's lymphoma.
A retrospective, multi-center analysis of treatment intensification for human immunodeficiency virus-positive patients with high-risk diffuse large B-cell lymphoma. [2019]This analysis reviews the response rate (RR), treatment toxicity and overall survival (OS) for human immunodeficiency virus (HIV)-positive patients with high-risk diffuse large B-cell lymphoma (DLBCL) and the impact of treatment intensification. Fifty patients, treated with either rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (n = 35) or cyclophosphamide, vincristine, doxorubicin, methotrexate/etoposide, ifosfamide, cytarabine (CODOX-M/IVAC) ± R (n = 15) chemotherapy, were included. Baseline characteristics did not differ between the two treatment groups. Forty-seven patients (94%) received rituximab and 48 (96%) received combination anti-retroviral therapy, with chemotherapy. The RR and treatment-related mortality were not significantly different between the two groups. Overall, 68% achieved complete remission. There were significantly more infections and non-hematological toxicities in the CODOX-M/IVAC ± R group. With a median follow-up of 28 months, 2-year progression-free survival (PFS) and OS are 68% and 70%, respectively, with no significant differences in remission duration, PFS or OS between the groups. In our cohort, the outcome for HIV-positive patients with high-risk DLBCL is favorable. Treatment intensification is feasible, but demonstrated no advantage over R-CHOP.
Current approaches to the treatment of non-Hodgkin's lymphoma. [2021]Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has long been a standard treatment for lymphoma. Improvements to the efficacy of this regimen can be made by increasing the doses of doxorubicin and cyclophosphamide, as in the chemotherapeutic regimen of doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP), and by reducing the standard dosing interval, as seen with the CHOP-14 regimen. Adding the immunotherapeutic agent rituximab (R) to either CHOP or ACVBP has been shown to improve outcomes significantly, such that six cycles of R-CHOP plus two cycles of ritux-imab are as effective as eight cycles of R-CHOP, and R-CHOP-21 appears to be at least as effective as the more dose-intense R-CHOP-14. In patients who have several adverse prognostic factors, R-ACVBP plus autologous stem-cell transplantation has been shown to produce good treatment outcomes. The use of positron emission tomography scanning before and early in treatment should allow prediction of long-term outcomes, and therefore the adaptation of treatment to individual prognosis and treatment needs. In patients with follicular lymphoma, rituximab has been shown to improve the efficacy of conventional chemotherapies. In addition, rituximab alone or yttrium-90-ibritumomab tiuxetan are effective maintenance therapies in this condition.
A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. [2019]Forty-one eligible patients with metastatic or recurrent carcinoma of the uterine cervix received 149 courses of carboplatin. The drug was administered at a starting dosage of 400 mg/m2 IV every 28 days. The overall response rate was 15% (two complete responses, four partial responses; 95% confidence interval 6-29%) and response durations were 2.0, 2.0, 2.5 +, 2.5+, 5.25 +, and 6.75 months. The major toxic effects included nausea and vomiting in 48% of courses, anemia in 47%, leukopenia in 38%, and thrombocytopenia in 22%. The activity of carboplatin against advanced cervical cancer is modest and similar to the activity of cisplatin alone. However, the toxicity profile of carboplatin is substantially better than that of cisplatin and warrants exploration of this agent against cervix cancer in more aggressive regimens or in combination with other agents.
Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer. [2013]Carboplatin, a cisplatin analog without significant clinical nephrotoxicity, has been evaluated in the treatment of 56 patients with small cell lung carcinoma at a dose of 300-400 mg/m2 iv monthly in a phase II study. Twenty-three patients (41%) achieved a response, including five (9%) complete remissions. Of 30 previously untreated patients, 18 (60%) achieved a response, including three (10%) complete remissions. Median response duration was 4.5 months (range, 2-9). No nephrotoxicity was seen and hydration was not required. Nausea or vomiting occurred in only 24 patients (43%) and was rarely severe. Myelosuppression was dose-limiting: 20 patients (36%) developed leukopenia and eight (14%) developed thrombocytopenia, but leukopenic infections occurred in only three patients. Carboplatin is a very active new agent in the treatment of small cell lung cancer, with less toxicity and better tolerance than cisplatin. It merits further investigation in combination chemotherapy and against non-small cell lung cancer.
Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. [2019]Combining cisplatin and carboplatin may eliminate some of the toxic effects of each agent and permit the use of higher doses, because these agents have different pharmacodynamics and dose-limiting toxicities. We investigated the safety and efficacy of these agents in combination. The toxicity profile was evaluated in a Phase I trial in 18 patients with advanced non-small cell lung cancer (NSCLC). Carboplatin was administered in doses ranging from 200 to 400 mg/m2 on day 1 and cisplatin at a dose of 80 mg/m2 on day 3. Only one cycle of chemotherapy was administered. Thrombocytopenia was the dose-limiting toxic effect. The maximal tolerated dose of carboplatin was 350 mg/m2. We then investigated the efficacy of the optimal dose of this combined chemotherapy in a Phase II trial in 13 patients. We used a carboplatin dose of 300 mg/m2 for safety in the Phase II trial. Three of 13 patients developed grade 3-4 hematologic toxicity, which was improved without major complications. A partial response was observed in 5 of 13 patients (38.5%). Combination chemotherapy with carboplatin (day 1, 300 mg/m2) and cisplatin (day 3, 80 mg/m2) showed promising effects in patients with advanced NSCLC.
Phase I study of carboplatin given on a five-day intravenous schedule. [2022]Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
Phase I and II agents in cancer therapy: two cisplatin analogues and high-dose cisplatin in hypertonic saline or with thiosulfate protection. [2019]Cisplatin is a chemotherapeutic coordination complex that has been evaluated extensively. It is particularly active against testicular cancer, but carcinomas of the ovary, bladder, cervix, and head and neck are also responsive. To increase efficacy and decrease toxicity, a number of platinum analogues have been developed and tested. One of these, carboplatin, is of particular interest. In clinical trials, it has demonstrated antitumor activity comparable to that of cisplatin, without evidence of significant renal toxicity or neurotoxicity. A second interesting platinum analogue is iproplatin. Preliminary phase I studies suggest reduced adverse renal and neurologic effects similar to those seen with carboplatin, with efficacy comparable to cisplatin. Attempts to overcome the dose-limiting toxicity of cisplatin by administering high-dose cisplatin (40 mg/m2/d for five days) in hypertonic saline or with thiosulfate protection are also reviewed. These techniques have eliminated nephrotoxicity as the dose-limiting toxicity of cisplatin. However, nonrenal toxicity, especially neurotoxicity, remains substantial. The extent to which high-dose cisplatin-based chemotherapy should be used in routine clinical practice has not been determined.
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]The safety and efficacy of rituximab with CODOX-M/IVAC (cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine) was retrospectively analysed in 23 patients with non-human immunodeficiency virus-related B-cell non-Hodgkin lymphoma with proliferation index >95% [14 with classical Burkitt lymphoma (BL), five with B-cell lymphoma unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and BL, and four with DLBCL]. Six (26%) low-risk (LR) patients received three cycles of CODOX-M and 17 (74%) high-risk (HR) cases were assigned to four cycles of alternating CODOX-M/IVAC. Rituximab 375 mg/m² was infused on days 1 and 10 of each cycle. Toxicity was comparable to that reported with CODOX-M/IVAC, with no treatment-related death. Two patients developed grade 3 rituximab-induced delayed neutropenia, with no adverse outcome. After completing treatment, 83% LR patients and 71% HR patients achieved CR by positron emission tomography-computerized tomography (PET-CT). Three (13%) patients received salvage treatment. At a median follow-up of 34 months (range = 18-75), 19 (83%) patients (100% LR and 74% HR) were alive, including one case undergoing salvage for late relapse. Four HR patients (17%) had died, three from primary progressive disease and one from treatment-refractory relapse 2 months after achieving CR. These results with R-CODOX-M/R-IVAC compare favourably with existing data using CODOX-M/IVAC and warrant further prospective studies. The potential pitfalls of PET-CT to assess response are highlighted.
Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. [2013]The Southwest Oncology Group has evaluated the activity of cis-dichlorodiammineplatinum(II) at a dose of 75 mg/m2 given as an iv bolus injection every 3 weeks to 25 fully and partially evaluable patients with advanced Hodgkin's disease and non-Hodgkin's lymphoma. One complete response, two partial responses, and one improvement less than a partial response were noted. Myelosuppression, in the form of leukopenia and thrombocytopenia, was identified and seemed to be more prevalent and more severe than in previous studies. We have attributed this to the extensive prior treatments which these patients had received and to the presence of tumor-bearing marrow which was observed in some of them. The anticipated toxic effects which were noted included nausea and vomiting, anorexia, diarrhea, renal injury, and hyperuricemia. The precise role of cis-dichlorodiammineplatinum(II) in the management of human lymphomas awaits elucidation.
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]We conducted a multi-center phase II trial of gemcitabine (G), carboplatin (C), dexamethasone (D), and rituximab (R) in order to examine its safety and efficacy as an outpatient salvage regimen for lymphoma. Fifty-one patients received 2-4 21-day cycles of G (1000 mg/m(2), days 1 and 8), C (AUC = 5, day 1), D (40 mg, daily days 1-4), and R (375 mg/m(2), day 8 for CD20-positive disease) and were evaluable for response. Characteristics included: median age 58 years (19-79 years), stage III/IV 88%, elevated LDH 33%, median prior therapies 2, prior stem cell transplant 12%, chemoresistant 62%, median prior remission duration 2.5 months. The overall and complete response rates were 67% (95% confidence interval [CI] 54-80%) and 31% (95% CI 19-44%), respectively, with activity seen in a broad variety of histologies. Responses occurred in 16 of 17 (94%, 95% CI 83-100%) transplant-eligible patients and 15 of 28 (54%, 95% CI 34-71%) with chemoresistant disease. The median CD34 yield in patients attempting peripheral blood stem cell (PBSC) collection following this regimen was 10.9 x 10(6) CD34+ cells/kg (range 5.0-24.1 x 10(6)). Hematologic toxicity was common, but febrile neutropenia (2.5%) and grade 4 non-hematologic adverse events (n = 2) were rare, with no treatment-related deaths. GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma, and successfully mobilizes PBSCs.