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

NCT05013437 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: CASE1A20
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Residual myeloma cell number measured by NGS

  Myeloma disease response will be assessed by residual myeloma cell number measured via NGS method, utilizing clonoSEQ (assay) before and after low dose Evomela. The clonoSEQ Assay measures minimal residual disease (MRD) to monitor changes in burden of disease during and after treatment. MRD refers to the number of MM cells that remain in a person during and following treatment.

  At baseline

• Residual myeloma cell number measured by NGS

  Myeloma disease response will be assessed by residual myeloma cell number measured via NGS method, utilizing clonoSEQ before and after low dose Evomela. The clonoSEQ Assay measures minimal residual disease (MRD) to monitor changes in burden of disease during and after treatment. MRD refers to the number of MM cells that remain in a person during and following treatment.

  After treatment, day 15

Secondary Outcomes (6)

• Toxicity in pre-transplant period assessed according to CTCAE v. 5.0

  Days 1, 8, 15, and 52

• Percent of participants with pre-transplant period safety

  Days 1, 8, 15, and 52

• Percent of participants with diarrhea and oral mucositis and other non-hematologic toxicities

  Day 52

• Percent of participants with post-transplant period safety

  Day 52

• Percent of participants with engraftment failure

  Day 52

Study Arms (1)

Evomela (Melphalan)

EXPERIMENTAL

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.

Drug: Evomela; Device: Next Generation Sequencing; Drug: Prochlorperazine; Drug: Acetaminophen; Drug: Diphenhydramine

Interventions

Evomela DRUG

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

Also known as: Melphalan

Evomela (Melphalan)

Next Generation Sequencing DEVICE

Next Generation Sequencing

Evomela (Melphalan)

Prochlorperazine DRUG

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

Evomela (Melphalan)

Acetaminophen DRUG

650 mg once orally within 30 minutes before Evomela

Evomela (Melphalan)

Diphenhydramine DRUG

50 mg once intravenously within 30 minutes before Evomela

Evomela (Melphalan)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Koen van Besien: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; High-Throughput Nucleotide Sequencing; Prochlorperazine; Acetaminophen; Diphenhydramine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Sequence Analysis; Genetic Techniques; Investigative Techniques; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Koen van Besien, MD, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Division Chief, Hematology and Cellular Therapy, UH Cleveland Medical Center

Study Record Dates

• First Submitted: August 13, 2021
• First Posted: August 19, 2021
• Study Start: September 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: March 1, 2024
• Last Updated: April 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

US (1)