Multiple Myeloma
Conditions
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.
Interventions
OTHERAscorbate
Ascorbate is in the vitamin drug class
DRUGMelphalan
Melphalan is an alkylating agent coupled to an amino acid
Sponsors
University of Iowa
Christopher Strouse
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment related adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 | 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
| Measure | Time frame | Description |
|---|---|---|
| Rate of minimal residual disease (MRD) negativity through bone marrow testing and imaging | 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. |
| Overall response rate based on International Myeloma Working Group (IMWG) criteria | Through 24 months after the end of treatment | Response to treatment will be assessed by IMWG criteria. |
| Categorize and quantify adverse events compared to historical control | 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. |
| Oxidative stress parameters in plasma through blood testing | Through 24 months after the end of treatment | Blood will be drawn and serum iron, TIBC, serum ferritin and transferrin saturation levels tested. |
Countries
United States
Outcome results
None listed