Ascorbic Acid and Chemotherapy for Relapsed or Refractory Lymphoma, CCUS, and CMML
This study is investigating if adding ascorbic acid (Vitamin C) to standard chemotherapy treatments like carboplatin, cisplatin, cytarabine, and dexamethasone can help patients with certain types of lymphoma that have returned or are not responding to treatment. It also looks at patients with clonal cytopenia of undetermined significance (CCUS) and chronic myelomonocytic leukemia (CMML). The goal is to see if ascorbic acid makes cancer cells more sensitive to chemotherapy, potentially killing more of them. The study aims to measure how many patients respond to the treatment. While 80 participants were planned, Arms A, B, C, and D are currently closed to new enrollment. You must be at least 18 years old and have biopsy-proven relapsed or refractory lymphoma to be considered.
- Study design
- This interventional study planned to enroll 80 participants. It compared ascorbic acid plus standard salvage therapy to standard salvage therapy plus normal saline in some groups.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Overall response rates were measured for up to 2 years, and hematologic response rates were measured at 20 weeks.
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NCT03418038
Ascorbic Acid and Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma, CCUS, and Chronic Myelomonocytic Leukemia
Recruiting
PHASE2Ages 18+InterventionalTreatmentMayo ClinicInvestigator-initiated
~80 participants
Updated 2026-04-16 on ClinicalTrials.gov
What's tested:Ascorbic AcidCarboplatinCisplatinCytarabineDexamethasoneEtoposide
At a glance
Recruiting sites
1 of 4 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall response rate (ORR) (Arms A and B)
Measured over Up to 2 years
+3 more outcomes measured
Conditions
Where it's being run
4 sites across 2 statesMinnesota2
Wisconsin2
Study leadership
- Thomas E Witzig, M.D. · PRINCIPAL_INVESTIGATOR · Mayo Clinic
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Age \>= 18 years
Biopsy-proven relapsed or refractory lymphomas; relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted \> 6 months; refractory is no response or relapse within 6 months; previous biopsies \< 6 months prior to treatment on this protocol will be acceptable
NOTE: Arms A/B - relapsed or refractory DLBCL within 24 months from the end of anthracycline-based therapy; no prior salvage therapy; patients can have received radiation therapy as part of initial treatment but not specifically for relapse
NOTE: Arm C patients include relapsed or refractory lymphoma patients of any type for which the recommended treatment includes one of the platinum-based regimens; of note, relapsed or refractory double-hit high grade lymphoma patients and relapsed or refractory Hodgkin lymphoma patients will be enrolled in Arm C; there is no limit on the number of prior therapies for Arm C patients; the patient must be eligible for a platinum-based regimen and must not have received the same regimen in the past without responding
Measurable or assessable disease: measurable disease is defined as measurable by computed tomography (CT) \[dedicated CT or the CT portion of a positron emission tomography (PET)/CT\] or magnetic resonance imaging (MRI): to be considered measurable, there must be at least one lesion that has a single diameter of \>= 1.5 cm
NOTE: Skin lesions can be used if the area is \>= 1.5 cm in at least one diameter and photographed with a ruler; patients with assessable disease by PET are also eligible as long as the assessable disease is biopsy proven lymphoma
Arms A/B - eligible for treatment with ifosfamide, carboplatin, and etoposide (+/- rituximab)
Arm C eligible for treatment with one of the following standard, every 3 week, platinum-based salvage regimens (with or without monoclonal antibody as appropriate for the disease):
Ifosfamide/carboplatin/etoposide (ICE) or rituximab/ifosfamide/carboplatin/etoposide (RICE);
Cisplatin, cytarabine (cytosine arabinoside), dexamethasone (DHAP) or RDHAP;
Gemcitabine hydrochloride (gemcitabine), dexamethasone, cisplatin (GDP) or rituximab, gemcitabine, dexamethasone, cisplatin (RGDP);
Gemcitabine and oxaliplatin (GemOx) or rituximab, gemcitabine and oxaliplatin (RGemOx);
Oxaliplatin, cytosine arabinoside, dexamethasone (OAD) or rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Hemoglobin \>= 8.0 g/dL (may transfuse to meet this requirement), obtained =\< 14 days prior to registration
Absolute neutrophil count (ANC) \>= 1500/mm\^3, obtained =\< 14 days prior to registration
Platelet count \>= 75000/mm\^3, obtained =\< 14 days prior to registration
Total bilirubin =\< 2 x upper limit of normal (ULN) (if \> 2 x ULN direct bilirubin is required and should be =\< 1.5 x ULN), obtained =\< 14 days prior to registration
Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3 x ULN (=\< 5 x ULN for patients with liver involvement), obtained =\< 14 days prior to registration
Creatinine =\< 1.6 mg/dL; if over 1.6 then the calculated creatinine clearance must be \>= 55 ml/min using the Cockcroft-Gault formula, obtained =\< 7 days prior to registration
Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Human immunodeficiency virus (HIV) test done =\< 14 days prior to registration
If positive, the CD4 count must be \> 400
Provide written informed consent
Willingness to have a central venous line \[peripherally inserted central catheter (PICC) or PORT\]
Willingness to provide mandatory blood specimens for correlative research
Willingness to provide mandatory tissue specimens for correlative research
Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Willingness to follow the requirements of the intravenous ascorbic acid program schedule
ARM D: Patients who had a diagnosis of CCUS with one or more TET2 mutations or TET2 mutations with concurrent splicing genes mutations (SRSF2, U2AF1, SF3B1, and ZRSR2) or epigenetic regulator mutations (DNMT3A, EZH2, IDH1, IDH2). CCUS diagnosis being defined based on the absence of definitive morphologic evidence of hematologic neoplasms from bone marrow biopsy evaluation combined with evidence of pathogenic myeloid somatic mutation with a variant allele frequency (VAF) of at least 2% using our institution's next generation sequencing (NGS) panel (OncoHeme, Mayo Clinic)
ARM D: ECOG performance status (PS) 0, 1 or 2
ARM D: Patients must meet at least 1 of these 3 laboratory criteria to be enrolled:
Hemoglobin =\< 10g/dL (obtained =\< 7 days prior to registration)
Absolute neutrophil count (ANC) =\< 1000/mm\^3 (obtained =\< 7 days prior to registration)
Platelet count =\< 100,000/mm\^ 3 (obtained =\< 7 days prior to registration)
ARM D: Total bilirubin =\< 2 x ULN (if \> 2 x ULN direct bilirubin is required and should be =\< 1.5 x ULN) (obtained =\<7 days prior to registration)
ARM D: Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3 x ULN (=\< 5 x ULN for patients with liver involvement) (obtained =\<7 days prior to registration)
ARM D: Creatinine =\< 1.6 mg/dL (obtained =\<7 days prior to registration). If \> 1.6, then the Calculated creatinine clearance must be \>= 55 ml/min using the Cockcroft-Gault formula
ARM D: Negative pregnancy test, for persons of childbearing potential only (obtained =\< 7 days prior to registration). NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
ARM D: Provide written informed consent
ARM D: Willingness to have a central venous line (PICC or PORT)
ARM D: Willingness to provide mandatory blood specimens for correlative research
ARM D: Willingness to return to enrolling institution (MCR) for follow-up (during the active monitoring phase of the study)
ARM D: Willingness to follow the requirements of the intravenous ascorbic acid program schedule
ARM E PRE-REGISTRATION: Age ≥ 18 years
ARM E PRE-REGISTRATION: New or an established diagnosis of 2016 World Health Organization (WHO) defined chronic myelomonocytic leukemia with a somatic TET2, IDH1, or IDH2 mutation requiring treatment with DNA methyltransferase inhibitors/hypomethylating agents
ARM E PRE-REGISTRATION: No prior CMML directed therapy.
Exception: Received ≤ 1 cycle of azacitidine, decitabine, erythropoiesis stimulating agent therapy (ESA), or oral decitabine and cedazuridine. NOTE: Prior exposure to hydroxyurea is allowed. Continuation beyond the first cycle must be discussed with the principal investigator (PI)
ARM E PRE-REGISTRATION: Creatinine ≤ 1.6 mg/dL. If \> 1.6, then the Calculated creatinine clearance must be ≥ 55 ml/min using the Cockcroft-Gault formula
ARM E PRE-REGISTRATION: Willingness to provide mandatory research bone marrow sample for correlative research
ARM E PRE-REGISTRATION: ECOG performance status (PS) 0, 1, or 2
ARM E PRE-REGISTRATION: Provide written informed consent
ARM E REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
ARM E REGISTRATION: Willingness to return to enrolling institution (MCR) for follow-up (during the active monitoring phase of the study)
ARM E REGISTRATION: Recovered to grade 1 or baseline or established as sequelae from all toxic effects of previous therapy except alopecia
ARM E REGISTRATION: Absolute neutrophil count (ANC) ≥ 500/mm\^3 (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Platelet count ≥ 20,000/mm\^3 (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Total bilirubin ≤ 1.5 x ULN ( ≤ 3 x ULN for patients with Gilbert's syndrome) (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Ability to complete questionnaire by themselves or with assistance
ARM E REGISTRATION: For a person of child-bearing potential (WOCBP): Must agree to use contraception or take measures to avoid pregnancy during the study. Adequate contraception is defined as follows:
Complete true abstinence
Consistent and correct use of one of the following methods of birth control:
Male partner who is sterile prior to the female patient's entry into the study and is the sole sexual partner for that female patient
Implants of levonorgestrel
Injectable progestogen
Intrauterine device (IUD) with a documented failure rate of less than 1% per year
Oral contraceptive pill (either combined or progesterone only)
Barrier method, for example: diaphragm with spermicide or condom with spermicide in combination with either implants of levonorgestrel or injectable progestogen
ARM E REGISTRATION: WOCBP must have a negative serum or urine pregnancy test ≤ 7 days prior to registration. NOTE: WOCBP include any person who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea \> 12 consecutive months); or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL. Even women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an IUD or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), must be considered to be of child-bearing potential. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
ARM E REGISTRATION: Persons who are able to father a child must use contraception during the study and for 3 months after the last treatment dose.
Complete true abstinence
Latex condom with a spermicidal agent
Diaphragm with spermicide
ARM E REGISTRATION: Willingness to have a central venous line (PICC or PORT)
ARM E REGISTRATION: Willingness to follow the requirements of the intravenous ascorbic acid program schedule
Exclusion
Any of the following:
Pregnant persons
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception
Any therapy =\< 2 weeks prior to registration; NOTE: Exception: patients on ibrutinib or corticosteroids (any dose) may continue therapy up until the new regimen has started at investigator discretion; corticosteroids can be tapered to lowest possible dose after start of treatment at investigator discretion. Exception: Palliative radiation is allowed
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Receiving any other investigational agent which would be considered as a treatment for the lymphoma
Other active malignancy than lymphoma
NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer that could interfere with this protocol therapy; patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria; patients with non-melanotic skin cancer may enroll
History of myocardial infarction =\< 6 months, or current symptomatic congestive heart failure or left ventricular ejection fraction (LVEF) \< 40% or with \> grade 2 diastolic dysfunction, with no symptoms or signs of heart failure
Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
Patients with active central nervous system (CNS) lymphoma or active cerebrospinal fluid (CSF) involvement with malignant cells requiring CNS-specific therapy with IV or intrathecal (IT) methotrexate (MTX); Note: Patients with any prior CNS lymphoma (parenchymal or leptomeningeal) MUST be in complete remission (CR) in those compartments without any maintenance therapy required
Patients with uncontrolled or symptomatic kidney stones
Known paroxysmal nocturnal hemoglobinuria (PNH)
ARM D: Bona-fide hematological neoplasm
ARM D: Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
Pregnant persons
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception
ARM D: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
ARM D: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
ARM D: History of myocardial infarction =\< 6 months, or current symptomatic congestive heart failure or known LVEF \< 40% or with \> grade 2 diastolic dysfunction, with no symptoms or signs of heart failure
ARM D: Patients with uncontrolled or symptomatic kidney stones
ARM D: Known paroxysmal nocturnal hemoglobinuria (PNH)
ARM D: Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
ARM E PRE-REGISTRATION: Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes other than CMML
ARM E PRE-REGISTRATION: Active central nervous system disease
ARM E PRE-REGISTRATION: Any active disease condition that would render the protocol treatment dangerous or impair the ability of the patient to receive study drug
ARM E PRE-REGISTRATION: Concurrent active malignancy, except adequately treated nonmelanoma skin cancer. History of curatively treated in situ cancer of the cervix, curatively treated in situ cancer of the breast, or other solid tumors curatively treated is allowed as long as there is no evidence of disease for \> 2 years
ARM E PRE-REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
ARM E PRE-REGISTRATION: Disease requiring systemic treatment with systemic immunosuppression with steroid steroids at a dose of ≥ 20 mg/day prednisone (or equivalent). Exceptions: Intermittent use of bronchodilators or inhaled steroids, local steroid injections, topical steroids
ARM E PRE-REGISTRATION: Patients with uncontrolled or symptomatic kidney stones
ARM E REGISTRATION: New York Heart Association (NYHA) class III/IV heart failure or active angina/angina equivalents
ARM E REGISTRATION: History of myocardial infarction ≤ 6 months, or current symptomatic congestive heart failure or known LVEF \< 40% or with \> grade 2 diastolic dysfunction, with no symptoms or signs of heart failure
ARM E REGISTRATION: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac arrhythmia, unstable angina pectoris, clinically significant nonhealing or healing wounds, pulmonary congestion or pulmonary edema, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection, clinical dehydration, or psychiatric illness/social situations that would limit compliance with study requirements
ARM E REGISTRATION: Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
ARM E REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
Pregnant persons
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception
What this trial measures
- Overall response rate (ORR) (Arms A and B)Up to 2 years
Defined as an objective status of complete response (CR) or partial response (PR) evaluated by Response Evaluation Criteria in Lymphoma (RECIL) criteria after 2 courses of treatment in all arms. Will be compared between the two arms. The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm. For the diffuse large B-cell lymphoma (DLBCL) arms, comparison of overall response rates between the two treatment groups will be performed using a one-sided chi-square test at significance level 0.10.
- ORR (Arm C)Up to 2 years
Defined as an objective status of CR or PR evaluated by RECIL criteria after 2 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm.
- Hematologic response (HI) rate (Arm D)At 20 weeks
Defined as an objective status of HI-E (minor or major response), HI-P, or HI-N evaluated by Myelodysplastic Syndrome International Working Group (IWIG) 2018 criteria at 20 weeks. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm.
- Overall Response Rate (ORR) in Arm EAt completion of cycle 4 (each cycle is 21 days)
Defined as an objective status of complete remission, complete cytogenetic remission, partial remission, bone marrow response, or clinical benefit after 4 cycles of therapy as defined by the 2015 IWG myelodysplastic syndrome/ myeloproliferative neoplasm response criteria.