What side effects are associated with this type of intervention?

Common treatments for Clonal Cytopenia, particularly those involving chemotherapy agents, can lead to side effects such as bone marrow suppression (resulting in leukopenia, thrombocytopenia, and anemia), gastrointestinal issues (nausea, vomiting, diarrhea), and an increased risk of infections. When ascorbic acid is used to enhance the sensitivity of cancer cells to chemotherapy, it generally does not add significant toxicity but the combination can still result in the typical side effects associated with chemotherapy.

What prior FDA approvals exist?

There is no specific mention of FDA approvals for the treatment of Clonal Cytopenia in the provided context. However, treatments that enhance the sensitivity of cancer cells to chemotherapy, such as the combination of ascorbic acid with chemotherapy, are being studied. Ascorbic acid is being investigated for its potential to make cancer cells more sensitive to chemotherapy, which could be beneficial in treating conditions like relapsed or refractory lymphoma, clonal cytopenia of undetermined significance, and chronic myelomonocytic leukemia (CMML).

What other types of research exist?

Promising novel alternatives to ascorbic acid for enhancing the sensitivity of cancer cells to chemotherapy in clonal cytopenia patients include the combination of 4-hydroperoxycyclophosphamide (4-HC) and cisplatin, which has shown cytotoxic synergism against leukemia cells. Additionally, the new anthracycline analogue 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin (MRA-CN) has demonstrated high potency and non-cross-resistance with doxorubicin, making it an attractive candidate for clinical trials.

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Chemotherapy

Ascorbic Acid + Chemotherapy for Lymphoma

Q: What is the mechanism of action of this treatment?

The most common treatments for Clonal Cytopenia often involve the use of chemotherapy drugs, which work by killing cancer cells, inhibiting their division, or preventing their spread. Ascorbic acid, or vitamin C, is being studied for its potential to enhance the sensitivity of cancer cells to these chemotherapy agents. This is significant for Clonal Cytopenia patients because increasing the effectiveness of chemotherapy can lead to more efficient eradication of abnormal cells, potentially improving patient outcomes and reducing the burden of the disease.

Phase 2

Recruiting

Led By Thomas E Witzig

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 18 years

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

Must not have

Bona-fide hematological neoplasm

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to high doses of vitamin C and typical chemotherapy effects like nausea, fatigue, hair loss, increased risk of infection due to low blood cell counts, kidney issues from certain drugs used in the regimen.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My kidney function, measured by creatinine levels, is within the required range.

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I was diagnosed with CCUS and have specific genetic changes.

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I am able to care for myself and perform daily activities.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with a blood cancer.

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

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I have been diagnosed with PNH.

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I am aware the study drug may affect my DNA and reproductive health.

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I have cancer other than lymphoma.

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I have a known G6PD deficiency.

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I have kidney stones that are not managed or cause symptoms.

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I do not have any severe illnesses that could interfere with the study.

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I have not had a heart attack in the last 6 months and my heart functions well.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Hematologic response (HI) rate (Arm D)

ORR (Arm C)

Overall Response Rate (ORR) in Arm E

+1 more

Secondary study objectives

Clinical benefit rate (Arm E)

Clinical benefit rate (Arms A, B, and C)

Continued salvage therapy beyond cycle 2 (Arm A, B and C)

+6 more

Other study objectives

Biomarker analysis (Arm D)

Biomarker analysis on blood and tissue (Arms A, B, and C)

Molecular response (Arm D)

+1 more

Side effects data

From 2016 Phase 2 & 3 trial • 86 Patients • NCT03002038

Gastrointestinal intolerance

Impaired liver function test

100%

80%

60%

40%

20%

Study treatment Arm

Azathioprine

Rituximab

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dexamethasone

2007

Completed Phase 4

~2650

Decitabine

2004

Completed Phase 3

~1680

Biospecimen Collection

2004

Completed Phase 3

~2020

Core Biopsy

2013

N/A

~130

Bone Marrow Aspiration

2011

Completed Phase 2

~1740

Bone Marrow Biopsy

2021

Completed Phase 3

~230

Echocardiography

2013

Completed Phase 4

~11580

Positron Emission Tomography

2011

Completed Phase 2

~2200

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Computed Tomography

2017

Completed Phase 2

~2740

Cytarabine

2016

Completed Phase 3

~3330

Gemcitabine Hydrochloride

2005

Completed Phase 3

~5420

Rituximab

1999

Completed Phase 4

~2990

Cisplatin

2013

Completed Phase 3

~3120

Oxaliplatin

2011

Completed Phase 4

~2890

Ascorbic Acid

2017

Completed Phase 4

~2280

Carboplatin

2014

Completed Phase 3

~6120

Etoposide

2010

Completed Phase 3

~2960

Ifosfamide

2010

Completed Phase 4

~3140

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Clonal Cytopenia often involve the use of chemotherapy drugs, which work by killing cancer cells, inhibiting their division, or preventing their spread. Ascorbic acid, or vitamin C, is being studied for its potential to enhance the sensitivity of cancer cells to these chemotherapy agents. This is significant for Clonal Cytopenia patients because increasing the effectiveness of chemotherapy can lead to more efficient eradication of abnormal cells, potentially improving patient outcomes and reducing the burden of the disease.

Effects of cyclophosphamide on murine bone marrow and splenic megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels.Differential effects of nitrostyrene derivatives on myelopoiesis involve regulation of C/EBPα and p38MAPK activity.Case of isolated thrombocytopenia due to cobalamin deficiency.