Melphalan on Disease Burden Measured by Next Generation Sequencing Before AHCT (Autologous Hematopoietic Cell Transplant) for Multiple Myeloma

Study Purpose

The purpose of this study is to see if Multiple Myeloma (MM) cells are sensitive to the chemotherapy used in transplant or not. The main chemotherapy agent utilized in stem cell transplant is melphalan. The study will utilize 1/10 of the dose used in transplant to study sensitivity of the tumor to melphalan. Melphalan is approved by the U.S. Food and Drug Administration (FDA) for transplant for MM patients.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Participants must have diagnosis of symptomatic MM.
  • - Participants must have received at least three cycles of anti-myeloma regimen including a proteasome inhibitor (i.e., bortezomib, carfilzomib or ixazomib) plus Lenalidomide or daratumumab, and have future plan of autologous stem cell transplant.
  • - Participants must have achieved Partial Response based on International Myeloma Working Group response criteria (Appendix II).
  • - Participants must have at least equal or greater than 100 mg/dL or 0.1 gr/dL monoclonal protein on serum electrophoresis and immunofixation at diagnosis.
  • - Minimum 3 x10^6/kg collected CD34+cells in one or multiple days.
(CD=cluster of differentiation)
  • - Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Life expectancy ≥ 12 months.
  • - Adequate hepatic function, as defined by: - Serum ALT ≤ 3.5 times the upper limit of normal (ALT=alanine aminotransferase) - Serum direct bilirubin ≤ 2 mg/dL (34 μmol/L) within 21 days prior to initiation of therapy.
  • - Creatinine clearance (CrCl) ≥ 40 mL/minute within 21 days prior to start of therapy either measured or calculated using a standard formula (e.g., Cockcroft and Gault).
  • - Adequate bone marrow function ,as defined by: - Hemoglobin ≥ 10.0 g/dl.
  • - WBC (white blood cell count) ≥ 3.00 x 10^9/L.
  • - Absolute neutrophil count ≥1.5 x10^9/L.
  • - Platelets ≥ 100 x 10^9/L ---Growth factors are not allowed to be used in order to meet adequate bone marrow function.
  • - Written informed consent in accordance with federal, local, and institutional guidelines.
  • - Participants of childbearing potential must agree to practice reliable contraception for at least 28 days before and for 60 days after last dose of study drug.
Reliable contraception is defined as:
  • - One highly effective method and one additional effective (barrier) method: - Examples of highly effective methods: - Intrauterine device (IUD)▪Hormonal (injections, implants, levonorgestrel releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g.desogestrel]) - Tubal ligation.
  • - Partner's vasectomy.
  • - Examples of additional effective methods.
  • - Male condom.
  • - Diaphragm.
  • - Cervical Cap.

Exclusion Criteria:

  • - Prior treatment toxicities have not resolved to ≤ Grade 2 according to NCI CTCAE Version 5.0 (except neuropathy).
  • - Participant receiving any other investigational agents within 21 days prior to study/treatment.
  • - Treatment with any anti-myeloma chemotherapy within 14 days.
  • - Diagnosis of amyloidosis, POEMS.
  • - Major surgery, radiotherapy or infection requiring therapy within 14 days of starting study treatment.
  • - History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan.
  • - Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • - Pregnant or breastfeeding women are excluded from this study because melphalan is an alkalizing agent with the potential for teratogenic or abortifacient effects.
Because there is unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with melphalan, breastfeeding should be discontinued if the mother is treated with melphalan.
  • - Unstable angina or myocardial infarction within 4 months prior to registration, NYHA (New York Heart Association) Class II, III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
  • - Cerebrovascular disease manifested as prior stroke at any time or TIA (transient ischemic attack) in the 12 months prior to initiation of therapy.
  • - Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
  • - Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05013437
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ehsan Malek
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Ehsan Malek, MD
Principal Investigator Affiliation University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

Currently, there is no method to predict whether a patient will have benefit from stem cell transplant or not. The usual approach is to proceed to stem cell transplant as long as a patient with MM has adequate organ function, meaning heart, kidney, lungs and other organs can tolerate the complications from transplant. In this study, all participants will already have had pre-collection bone marrow aspirate as standard of care that will be available for minimal residual disease (MRD) testing by NGS platform. Participants will receive only one, low-dose of melphalan (Evomela) intravenously. Participants will be asked to return to clinic for a follow-up visit at one week and two weeks after the infusion. Another bone marrow aspirate will be performed after 2 weeks from the day of Evomela administration. After the study, participants will have a standard-of-care (SOC) autologous stem cell transplant. The primary objective is to evaluate the impact of a test dose of low dose melphalan (16 mg/m2) before autologous hematopoietic cell transplant on disease volume measured by Next Generation Sequencing (NGS). Secondary objectives are:

  • - To assess safety of low dose melphalan after CD34 (cluster of differentiation 34) collection and before high-dose melphalan-based autologous stem cell transplant.
  • - To describe the impact of a test dose of low dose melphalan (16 mg/m2) before autologous hematopoietic cell transplant on disease volume measured by peripheral blood Mass Spectrometry.

Arms & Interventions

Arms

Experimental: Evomela (Melphalan)

Participants will receive Evomela 16 mg/m2 on day 1 of the study only. Evomela will be given as IV infusion over 30 minutes after administration of 500 cc normal saline as pre-hydration and pre-medications Prochlorperazine, Acetaminophen, and Diphenhydramine.

Interventions

Drug: - Evomela

16 mg/m^2 Evomela administered one time via a central line

Device: - Next Generation Sequencing

Next Generation Sequencing

Drug: - Prochlorperazine

10mg once intravenous (IV) within 30 minutes before Evomela

Drug: - Acetaminophen

650 mg once orally within 30 minutes before Evomela

Drug: - Diphenhydramine

50 mg once intravenously within 30 minutes before Evomela

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Cleveland, Ohio

Status

Recruiting

Address

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106

Site Contact

Ehsan Malek, MD

CTUReferral@UHhospitals.org

800-641-2422