Melphalan before Stem Cell Transplant for the Treatment of Multiple Myeloma
Multiple Myeloma
Plasma cell neoplasm
18 Years and older, Male and Female
WINSHIP5001-20 (primary)
NCI-2020-04920
STUDY00000449
Summary
This phase I trial studies the best dose and side effects of melphalan in treating patients with multiple myeloma who are undergoing stem cell transplant. Chemotherapy drugs, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial uses a new method of dosing that is based on analysis of each individual’s blood levels of melphalan after receiving a part of the dose, termed pharmacokinetic analysis. This may help to learn more about how to dose melphalan correctly and which patients are likely to benefit from a personalized dose.
Objectives
PRIMARY OBJECTIVES:
I. Measure achievement of target melphalan systemic exposure in the first 20 patients.
II. Identify safety and preliminary efficacy within each systemic exposure range of melphalan using a 5+5 design.
SECONDARY OBJECTIVES:
I. Describe International Myeloma Working Group response levels and selected grade 3/4 toxicities in an expansion set of patients at the recommended phase 2 area under the curve (AUC) range.
II. Measure deoxyribonucleic acid (DNA) repair score from formalin-fixed paraffin-embedded diagnostic bone marrow sample (FFPE) and from pretransplant marrow aspirate sample.
III. Assess melphalan-induced DNA damage in peripheral blood mononuclear cells (PBMCs) from melphalan-treated patients.
IV. To correlate peripheral blood circulating multiple myeloma cells (CMMCs) numbers obtained with (CELLSEARCH) with minimal residual disease (MRD) assessment at day +90.
OUTLINE: This is a dose-escalation study.
Patients receive standard of care high dose melphalan hydrochloride intravenously (IV) over 30 minutes on day -3 and PK-directed melphalan hydrochloride IV over 30 minutes on day -1. Patients then undergo autologous stem cell transplantation (ASCT) on day 0.
After completion of study treatment, patients are followed up at 7, 14, 30, 60, and 90 days.
Eligibility
- Patient must have the clinical diagnosis of a plasma cell neoplasm requiring treatment per the treating physician using the International Myeloma Working Group (IMWG) and World Health Organization (WHO) criteria as guidelines. This can include extraosseous plasmacytoma, monoclonal immunoglobulin deposition disease, and heavy-chain diseases as these diagnoses, while rare, can be treated in part with autologous transplant
- If enrolling in phase A of this protocol, the patient
* Must have received 2+ lines of therapy as defined by the IMWG; and
* Must have estimated glomerular filtration rate (eGFR) by Cockcroft-Gault > 40 mL/min; and
* Be eligible and appropriate per the treating physician to receive 200 mg/m^2
** If enrolling in phase B of the protocol, the transplant must be part of first line therapy to provide some level of homogeneity for toxicity assessment and preliminary efficacy
- Absolute neutrophil count (ANC) >= 1000/uL
- Platelet count >= 100,000
- Total bilirubin < 1.5 x institutional upper limit of normal (unless the patient has an established diagnosis of Gilbert’s in which case total bilirubin < 3 mg/dL)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the institutional upper limit of normal
- Left ventricular ejection fraction >= 45%
- Diffusion capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) > 50% of predicted value (corrected for hemoglobin)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) is required for eligibility. Those patients with lower performance status based solely on bone pain secondary to multiple myeloma are eligible
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy. The effects of protocol therapy on the developing human fetus are unknown. For this reason, FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of protocol therapy administration. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Ability to understand and the willingness to sign a written informed consent document
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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