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Ascorbic Acid and Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma, CCUS, and Chronic Myelomonocytic Leukemia

ConditionsClonal Cytopenia of Undetermined SignificanceHigh Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRecurrent Diffuse Large B-Cell LymphomaRecurrent Hodgkin LymphomaRecurrent LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory LymphomaChronic Myelomonocytic Leukemia
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ascorbic Acid

    Dietary supplement

    Given IV

  • Carboplatin

    Drug

    Given IV or PO

  • Cisplatin

    Drug

    Given IV or PO

  • Cytarabine

    Drug

    Given IV or PO

  • Dexamethasone

    Drug

    Given IV or PO

  • Etoposide

    Drug

    Given IV or PO

  • Gemcitabine Hydrochloride

    Drug

    Given IV or PO

  • Ifosfamide

    Drug

    Given IV or PO

  • Laboratory Biomarker Analysis

    Other intervention

    Correlative studies

  • Oxaliplatin

    Drug

    Given IV or PO

  • Placebo Administration

    Other intervention

    Given normal saline IV

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Rituximab

    Biological/Vaccine

    Given IV

  • Decitabine

    Drug

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Core Biopsy

    Procedure/Surgery

    Undergo core needle biopsy

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration and biopsy

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow aspiration and biopsy

  • Echocardiography

    Procedure/Surgery

    Undergo ECHO

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Central Venous Cannula Insertion

    Procedure/Surgery

    Undergo PICC placement

  • Portacath Placement

    Procedure/Surgery

    Undergo portacath placement

  • Computed Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Decitabine and Cedazuridine

    Drug

    Given PO

Treatment groups

80 Participants
are divided into 5 treatment groups
Group A: Arm A (ascorbic acid, combination chemotherapy) - closed to enrollmentExperimental treatment 18 interventions
Group B: Arm B (placebo, combination chemotherapy) - closed to enrollmentActive comparator 18 interventions
Group C: Arm C (ascorbic acid and combination chemotherapy) - closed to enrollmentExperimental treatment 19 interventions
Group D: Arm D (ascorbic acid) - closed to enrollmentExperimental treatment 8 interventions
Group E: ARM E (ascorbic acid, decitabine)Experimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 2 years
2

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.

Time frame
Up to 2 years
3

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.

Time frame
At 20 weeks
4

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.

Time frame
At completion of cycle 4 (each cycle is 21 days)

Secondary outcomes

1

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

Will be estimated in each arm by the number of patients who achieve a CR, PR, minor response (MR), or stable disease (SD) on the cycle 2 response assessment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated. The clinical benefit rate will be compared between the DLBCL arms using the chi-square test (or Fisher's exact test if the data in the contingency table is sparse).

Time frame
Up to 2 years
2

Overall survival

The distribution of overall survival will be estimated in each arm using the method of Kaplan-Meier. In the DLBCL arms, the comparison of overall survival between the two treatment arms will be based on the log-rank test.

Time frame
From registration to death due to any cause, assessed up to 2 years
3

Progression-free survival

The distribution of progression-free survival will be estimated in each arm using the method of Kaplan-Meier. In the DLBCL arms, the comparison of progression-free survival between the two treatment arms will be based on the log-rank test.

Time frame
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
4

Percent of transplant eligible patients proceeding to transplant (Arms A, B and C)

Will be estimated in each arm by the number of patients proceeding to transplant divided by the total number of patients who were considered transplant eligible. Exact binomial 95% confidence intervals for the true success rate will be calculated. The rate will be compared between the DLBCL arms using the chi-square test (or Fisher's exact test if the data in the contingency table is sparse).

Time frame
Up to 2 years

Other outcomes

1

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

Will consider the correlative research exploratory.

Time frame
Baseline up to 2 years
2

Biomarker analysis (Arm D)

Variant allele frequency (VAF), biomarkers levels from Olink study, values of the cytokines, endothelial dysfunction, inflammation markers and levels of 5mc/5hmc will be measured at baseline, after completion of treatment (at 20 weeks), and at one-year post-registration. Values will be summarized graphically and descriptively at each time point and changes across time will be explored. Due to small sample size, these correlative analyses will be considered exploratory.

Time frame
Baseline up to 2 years
3

Molecular response (Arm D)

Defined as a 2 standard deviation reduction in VAF from baseline VAF. Exact binomial 95% confidence intervals for the true success rate will be calculated.

Time frame
Up to 2 years
4

TET2 activity (Arm D)

Values will be summarized graphically and descriptively at each time point and changes across time will be explored.

Time frame
At baseline and weeks 12, 20, 52

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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