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High Dose Ascorbic Acid for Plasma Cell Disorders

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ClinicalTrials.gov Identifier: NCT03602235
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : April 8, 2019
Sponsor:
Collaborator:
University of Iowa
Information provided by (Responsible Party):
Yogesh Jethava, University of Iowa

Brief Summary:
This is a Phase I single-arm open-label clinical study primarily assessing the safety and secondarily, the relative efficacy of low dose melphalan + high dose ascorbate acid (HDAA) in relapsed refractory patients with multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Other: Ascorbate Drug: Melphalan Phase 1

Detailed Description:
In this study, patients will be treated with low dose melphalan and 4 doses of HDAA for one cycle only. In total, 9 patients will be enrolled in this study. Bone marrow examination and imaging with PET and/or MRI will be performed 4 weeks from last dose of HDAA. Patients will be regularly followed up.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High Dose Ascorbic Acid (HDAA) in Patients With Plasma Cell Disorders
Actual Study Start Date : March 5, 2019
Estimated Primary Completion Date : May 11, 2020
Estimated Study Completion Date : May 11, 2021


Arm Intervention/treatment
Experimental: Low dose melphalan + high dose ascorbate acid (HDAA)

Patients will receive a test dose of 15g of HDAA prior to starting treatment dose. This will be mainly to rule out allergic reactions.

HDAA + Melphalan:

HDAA on day 1 and day 4 in combination with melphalan 12.5 mg/m2, followed by 2 additional doses of HDAA on day 2 and day 5.

A 3 + 3 cohort method will be used for this study. After successfully completing the test dose, subjects will receive 50gms, 75gms and 100gms of ascorbate per infusion in 3 different cohorts. Dose modifications are not made for weight or body surface area.

Other: Ascorbate
Ascorbate is in the vitamin drug class
Other Name: Ascorbate Acid; Ascorbic Acid for Injection, USP

Drug: Melphalan
Melphalan is an alkylating agent coupled to an amino acid
Other Name: L-phenylamine mustard; L-PAM; L-Sarcolysin




Primary Outcome Measures :
  1. Number of treatment related adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 [ Time Frame: First day of treatment through 28 days ]
    Adverse events occuring within the DLT assessment window which do not resolve in less than 72 hours and are not clearly and incontrovertibly due to extraneous causes.


Secondary Outcome Measures :
  1. Rate of minimal residual disease (MRD) negativity through bone marrow testing and imaging [ Time Frame: Through 28 days after the end of treatment ]
    MRD will be determined by highly sensitive, eight color flow on bone marrow sample. Functional imaging, such as PET scan and MRI will also be performed to assess the disease status.

  2. Overall response rate based on International Myeloma Working Group (IMWG) criteria [ Time Frame: Through 24 months after the end of treatment ]
    Response to treatment will be assessed by IMWG criteria.

  3. Categorize and quantify adverse events compared to historical control [ Time Frame: Up to 24 months following the end of treatment for the last patient ]
    The number and severity of all adverse events will be summarized by simple descriptive statistics and compared to a historical control.

  4. Oxidative stress parameters in plasma through blood testing [ Time Frame: Through 24 months after the end of treatment ]
    Blood will be drawn and serum iron, TIBC, serum ferritin and transferrin saturation levels tested.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has provided informed consent.
  2. Patients who have been previously treated with 3 lines of therapy, i.e. proteasome inhibitors, immuno-modulatory agents such as lenalidomide and monoclonal antibodies such as daratumumab, and have progressed within past 6 months. Participants with previous failed autologous transplant and progressed within 6 months after autologous transplant. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen.
  3. Patients have failed treatment with, are intolerant to or are not candidates for available therapies that are known to confer clinical benefit to patients with relapsed and refractory MM.
  4. Subjects must have measurable disease (as determined by the central lab), including at least one of the criteria below:

    • M-protein quantities ≥ 0.5 g/dl by SPEP or
    • ≥ 200 mg/24 hour urine collection by UPEP or
    • serum free light chain levels > 100 mg/L (milligrams/liter involved light chain) and an abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine m-protein or
    • For patients with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 500 mg/dL.

    Non-secretory participants are eligible provided the participant has > 20% bone marrow plasmacytosis OR multiple (≥3) plasmacytomas or lesions on MRI at the time of diagnosis or study enrollment, OR the presence of lesions (≥ 3) on PET/CT scan.

  5. Adequate organ function:

    • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L without growth factor support for 7 days (14 days if pegfilgastrim)
    • Platelets (plt) ≥ 50 x 109/L without transfusion for 7 days
    • Potassium within normal limits or correctable with supplements
    • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN)
    • Serum bilirubin ≤ 1.5 x ULN
    • Estimated serum creatinine clearance of ≥ 45 mL/min using the Cockcroft-Gault equation or directly calculated from the 24-hour urine collection method
    • International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
    • Ejection fraction by ECHO or MUGA of ≥ 40% performed.
    • Participants must have adequate pulmonary function studies (PFTs), > 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity ( DLCO) > 50% of predicted (adjusted for hemoglobin). If the participant is unable to complete PFTs due to disease-related pain or other circumstances that make it difficult to reliably perform PFTs, documentation of pulmonary function adequate for transplant will occur via a CT scan without evidence of major pulmonary disease, and arterial blood gas results.
  6. Participants must have a performance status of 0-2 based on ECOG criteria. Participants with poor performance status (3-4) based solely on bone pain will be eligible, provided there is documentation to verify this.
  7. Negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening.

Exclusion Criteria:

  1. Prior allogeneic transplant.
  2. Known hypersensitivity or allergy to ascorbic acid or melphalan.
  3. Participants must not have a concurrent malignancy unless it can be adequately treated by non-chemotherapeutic intervention. Participants may have a history of prior malignancy, provided that he/she has not had any chemotherapy within 365 days of study entry AND that life expectancy exceeds 5 years at the time of study entry.
  4. Participants must not have life-threatening comorbidities.
  5. History or evidence of myeloma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
  6. Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).
  7. Evidence of CNS myeloma.
  8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, recent (within 6 months) myocardial infarction, uncontrolled or symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension on appropriate therapy or psychiatric illness/social situations that would limit compliance with study requirements.
  9. Concurrent use of Coumadin (warfarin)
  10. Patients with G6PD deficiency
  11. Patients with a history of oxalate renal stones or a known history of multiple renal stones
  12. Diabetic patients who rely on a glucometer to dose insulin as ascorbate can interfere with glucometer readings

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03602235


Contacts
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Contact: Yogesh Jethava, MD 319-384-9067 yogesh-jethava@uiowa.edu

Locations
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United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Yogesh Jethava, MD    319-384-9067    yogesh-jethava@uiowa.edu   
Sponsors and Collaborators
Yogesh Jethava
University of Iowa
Investigators
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Principal Investigator: Yogesh Jethava, MD University of Iowa

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Responsible Party: Yogesh Jethava, Clinical Associate Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT03602235     History of Changes
Other Study ID Numbers: 201804754
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Ascorbic Acid
Melphalan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antioxidants
Protective Agents
Vitamins
Micronutrients
Nutrients
Growth Substances