Ascorbic Acid and Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma, CCUS, and Chronic Myelomonocytic Leukemia
Phase2 Trial of High Dose Intravenous Ascorbic Acid as an Adjunct to Salvage Chemotherapy in Relapsed/ Refractory Lymphoma, Patients With Clonal Cytopenia of Undetermined Significance, and Chronic Myelomonocytic Leukemia
4 other identifiers
interventional
80
1 country
4
Brief Summary
This phase II trial studies the effect of ascorbic acid and combination chemotherapy in treating patients with lymphoma that has come back (recurrent) or does not respond to therapy (refractory), clonal cytopenia of undetermined significance and chronic myelomonocytic leukemia (CMML). Ascorbic acid may make cancer cells more sensitive to chemotherapy. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ascorbic acid and combination chemotherapy may kill more cancer cells. Arms A, B, C, and D are closed to enrollment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2018
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2018
CompletedFirst Posted
Study publicly available on registry
February 1, 2018
CompletedStudy Start
First participant enrolled
March 23, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 22, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 2, 2033
April 16, 2026
April 1, 2026
12.9 years
January 25, 2018
April 13, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Overall response rate (ORR) (Arms A and B)
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.
Up to 2 years
ORR (Arm C)
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.
Up to 2 years
Hematologic response (HI) rate (Arm D)
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.
At 20 weeks
Overall Response Rate (ORR) in Arm E
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.
At completion of cycle 4 (each cycle is 21 days)
Secondary Outcomes (10)
Clinical benefit rate (Arms A, B, and C)
Up to 2 years
Overall survival
From registration to death due to any cause, assessed up to 2 years
Progression-free survival
From date of first treatment to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years
Percent of transplant eligible patients proceeding to transplant (Arms A, B and C)
Up to 2 years
Transfusion dependency (Arm D)
Up to 2 years
- +5 more secondary outcomes
Other Outcomes (4)
Biomarker analysis on blood and tissue (Arms A, B, and C)
Baseline up to 2 years
Biomarker analysis (Arm D)
Baseline up to 2 years
Molecular response (Arm D)
Up to 2 years
- +1 more other outcomes
Study Arms (5)
Arm A (ascorbic acid, combination chemotherapy) - closed to enrollment
EXPERIMENTALPatients 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.
Arm B (placebo, combination chemotherapy) - closed to enrollment
ACTIVE COMPARATORPatients 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.
Arm C (ascorbic acid and combination chemotherapy) - closed to enrollment
EXPERIMENTALPatients 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.
Arm D (ascorbic acid) - closed to enrollment
EXPERIMENTALPatients 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.
ARM E (ascorbic acid, decitabine)
EXPERIMENTALPatients 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.
Interventions
Given IV or PO
Given IV or PO
Correlative studies
Given IV or PO
Given normal saline IV
Given IV
Given IV
Undergo blood sample collection
Undergo core needle biopsy
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Undergo ECHO
Undergo PET/CT
Undergo MRI
Undergo portacath placement
Undergo PET/CT
Given IV
Given IV or PO
Given IV or PO
Given IV or PO
Given IV or PO
Given IV or PO
Undergo PICC placement
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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
- +62 more criteria
You may not qualify if:
- 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)
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
- National Cancer Institute (NCI)collaborator
Study Sites (4)
Mayo Clinic Health Systems-Mankato
Mankato, Minnesota, 56001, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, 54701, United States
Mayo Clinic Health System-Franciscan Healthcare
La Crosse, Wisconsin, 54601, United States
Related Publications (1)
Xie Z, Fernandez J, Lasho T, Finke C, Amundson M, McCullough KB, LaPlant BR, Mangaonkar AA, Gangat N, Reichard KK, Elliott M, Witzig TE, Patnaik MM. High-dose IV ascorbic acid therapy for patients with CCUS with TET2 mutations. Blood. 2024 Dec 5;144(23):2456-2461. doi: 10.1182/blood.2024024962.
PMID: 39352751DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Thomas E Witzig, M.D.
Mayo Clinic
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 25, 2018
First Posted
February 1, 2018
Study Start
March 23, 2018
Primary Completion (Estimated)
February 22, 2031
Study Completion (Estimated)
November 2, 2033
Last Updated
April 16, 2026
Record last verified: 2026-04