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Official Title
Phase 1 of Exposure Targeted Melphalan Dosing
Phase
Phase 1
Sponsor
Emory University
Enrollment
90
Timeline
May 2021 → Dec 2026
About This Study
This phase I trial studies the best dose and side effects of mephalan in treating patients with multiple myeloma who are undergoing stem cell transplant. Chemotherapy drugs, such as mephalan, 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.
Eligibility Criteria
Inclusion Criteria
- 1Patient 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
- 2If enrolling in phase A of this protocol, the patient
- 3must have received 2+ lines of therapy as defined by the IMWG; and
- 4Must have estimated glomerular filtration rate (eGFR) by Cockcroft-Gault \> 40 mL/min; and
- 5Be eligible and appropriate per the treating physician to receive 200 mg/m\^2
- 6If 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
- 7Absolute neutrophil count (ANC) \>= 1000/uL
- 8Platelet count \>= 100,000
- 9Total 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)
- 10Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x the institutional upper limit of normal
- 11Left ventricular ejection fraction \>= 45%
- 12Diffusion 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)
- 13Eastern 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
- 14Females 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. 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)
- 15The patient must be willing to comply with fertility requirements
- 16Ability to understand and the willingness to sign a written informed consent document
- 17Patients 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
Exclusion Criteria
- 1Patients known to meet criteria for progressive disease or clinical relapse between screening and planned melphalan infusion day -3
- 2Subject has any of the following cardiac abnormalities
- 3History of clinically significant cardiovascular disease with New York Heart Association class III or IV congestive heart failure or
- 4Severe non-ischemic cardiomyopathy or
- 5Myocardial infarction within the previous 6 months prior to starting study treatment
- 6Unstable or poorly controlled angina
- 7Uncontrolled severe hypertension
- 8Clinically/hemodynamically significant arrythmias
- 9Severe uncontrolled cardiac arrhythmias (grade 3 or higher) or
- 10Clinically significant electrocardiogram (ECG) abnormalities includingcorrected QT interval (QTc) \> 480 msec
- 11Human immunodeficiency virus (HIV) positive EXCEPT if the patient meets all the following: CD4 \> 350 cells/mm\^3, undetectable viral load, maintained on modern therapeutic regimen utilizing non CYP interacting agents (e.g. excluding ritonavir), and no untreated acquired immune deficiency syndrome defining opportunistic infections.
- 12Seropositive for hepatitis B surface antigen \[HBsAg\]) EXCEPT subjects with resolved infection (ie, subjects who are positive for antibodies to hepatitis B core antigen \[antiHBc\] and/or antibodies to hepatitis B surface antigen \[antiHBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. Subjects with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
- 13Seropositive for hepatitis C except in the setting of a sustained virologic response \[SVR\], defined as without viremia for at least 12 weeks after completion of antiviral therapy
- 14Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS) syndrome, amyloid light-chain (AL) amyloidosis, and Waldenstrom macroglobulinemia
- 15Concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
- 16Known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments
- 17Pregnant women are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to protocol treatment of the mother, breastfeeding should be discontinued
Locations
2 sites participating in this study
Winship Cancer Institute of Emory University
Atlanta, Georgia 30322
Craig C Hofmeister, MD, MPH
University Illinois Chicago
Chicago, Illinois 60607
Karen Sweiss, PharmD
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →