Multiple Myeloma Clinical Trial

High Dose Ascorbic Acid for Plasma Cell Disorders

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.

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Full 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.

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Eligibility Criteria

Inclusion Criteria:

Subject has provided informed consent.
Patients who have been previously treated with 3 or more lines of therapy, i.e. proteasome inhibitors, immuno-modulatory agents such as lenalidomide and treatment-should-you-receive-monoclonal-antibodies/" >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.

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.

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. However, patient can be enrolled if the ANC and platelets are low due to disease
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 or ≥30 mL allowed if renal insufficiency is attributed to myeloma.
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.
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.
Negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening.

Exclusion Criteria:

Prior allogeneic transplant.
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 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.
Participants must not have life-threatening comorbidities.
History or evidence of myeloma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).
Evidence of CNS myeloma.
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

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

9

Study ID:

NCT03602235

Recruitment Status:

Recruiting

Sponsor:

Michael Tomasson

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There is 1 Location for this study

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University of Iowa Hospitals and Clinics
Iowa City Iowa, 52242, United States More Info
Michael Tomasson, MD
Contact
319-335-4958
[email protected]

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

9

Study ID:

NCT03602235

Recruitment Status:

Recruiting

Sponsor:


Michael Tomasson

How clear is this clinincal trial information?

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