Overview
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.
Principal investigator
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
* 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
For Referring Providers
Do you have a patient you think would be a good candidate for this trial? Learn more about enrolling your patient.