Clinical trial NCT03602235: High Dose Ascorbic Acid for Plasma Cell Disorders
Official title: High Dose Ascorbic Acid (HDAA) in Patients With Plasma Cell Disorders
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: University of Iowa
First posted: 2018-07-26
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is a phase 1 study for patients with relapsed refractory multiple myeloma. Patients will receive a 15-gram test dose, and a maximum of 3 cycles, each composed of 4 doses of high-dose ascorbic acid (HDAA) and 2 doses of melphalan. This study will enroll 9 patients with relapsed refractory multiple myeloma. The starting dose of ascorbic acid will be 50 grams. Using a 3+3 dose escalation, the dose will potentially increase to 75 grams then 100 grams.

Eligibility criteria: Inclusion Criteria:

* Subject has provided informed consent.
* Diagnosis of multiple myeloma per IMWG criteria(26)
* Patients must have progressive disease following 3 or more prior lines of therapy.

  * Prior treatment must include a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.
  * Patients must not be candidates for regimens known to provide clinical benefit in relapsed or refractory multiple myeloma based on the investigator's judgement.
  * If a patient declines such therapy, this must be recorded in the study files. 4. Subjects must have measurable disease, including at least one of the criteria below:
  * SPEP demonstrating M-protein quantities ≥ 0.5 g/dl
  * UPEP demonstrating monoclonal protein ≥ 200 mg/24hr
  * Involved serum free light chain levels \> 100 mg/L and an abnormal kappa/lambda (κ/λ)ratio
  * 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 will qualify as measurable disease
  * Non-secretory participants are eligible provided the participant has \> 20% bone marrow plasmacytosis
* Adequate organ function:

  * Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L without growth factor support for 7 days
  * Platelets (plt) ≥ 50 x 10\^9/L without transfusion for 7 days.
  * Hemoglobin ≥ 8.0 g/dl, transfusion support permitted
  * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0x 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
  * Left Ventricular Ejection Fraction by ECHO or MUGA of ≥ 40%.
  * Participants must have a performance status of 0-2 based on ECOG criteria.
  * For people of child bearing potential negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening

Exclusion Criteria

* Known hypersensitivity or allergy to ascorbic acid or melphalan
* 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 they have not had any chemotherapy within 365 days of study entry AND their life expectancy exceeds 5 years with respect to the concurrent malignancy at the time of study entry.
* Participants must not have life-threatening comorbidities.
* Known human immunodeficiency virus(HIV) disease (requires negative test for clinically suspected HIV infection).
* 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.
* Concurrent use of Coumadin (warfarin)
* Patients with G6PD deficiency
* Patients with a history of oxalate renal stones or a known history of multiple renal stones
* Diabetic patients who rely on a glucometer to dose insulin as ascorbate can interfere with glucometer readings

Primary outcomes:
measure: Number of treatment related adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
timeFrame: First day of treatment through 28 days
Secondary outcomes:
measure: Rate of minimal residual disease (MRD) negativity through bone marrow testing and imaging
timeFrame: Through 28 days after the end of treatment
measure: Overall response rate based on International Myeloma Working Group (IMWG) criteria
timeFrame: Through 24 months after the end of treatment
measure: Categorize and quantify adverse events compared to historical control
timeFrame: Up to 24 months following the end of treatment for the last patient
measure: Oxidative stress parameters in plasma through blood testing
timeFrame: Through 24 months after the end of treatment
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Christopher Strouse, MD
role: PRINCIPAL_INVESTIGATOR
References: