Multiple MyelomaEarly Phase 1AHCTNCT05013437
Melphalan on Disease Burden Measured by Next Generation Sequencing Before AHCT (Autologous Hematopoietic Cell Transplant) for Multiple Myeloma
A Early Phase 1 study testing Evomela, Next Generation Sequencing and Prochlorperazine in people with Multiple Myeloma, run by Koen van Besien at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Evomela, Next Generation Sequencing and Prochlorperazine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2023to Mar 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
About this study
Official title: A Pilot Study to Assess Impact of Low Dose Melphalan on Disease Burden Measured by Next Generation Sequencing Before Autologous Hematopoietic Cell Transplant (AHCT) for Multiple Myeloma Patients
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.
Read the detailed description
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.
- Conditions
- Multiple Myeloma
- Being tested
- Evomela, Next Generation Sequencing, Prochlorperazine, Acetaminophen, Diphenhydramine
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvomelaDrug
Also called Melphalan
16 mg/m^2 Evomela administered one time via a central line
Next Generation SequencingDevice
Next Generation Sequencing
ProchlorperazineDrug
10mg once intravenous (IV) within 30 minutes before Evomela
AcetaminophenDrug
650 mg once orally within 30 minutes before Evomela
DiphenhydramineDrug
50 mg once intravenously within 30 minutes before Evomela
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Evomela; Device: Next Generation Sequencing; Drug: Prochlorperazine; Drug: Acetaminophen; Drug: Diphenhydramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: After treatment, day 15
Secondary outcomes (6)
Toxicity in pre-transplant period assessed according to CTCAE v. 5.0
Toxicity in pre-transplant period assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.
Measured: Days 1, 8, 15, and 52
Percent of participants with pre-transplant period safety
Safety will be assessed by absence of any grade 4 or 5 clinically relevant therapy-related toxicity, or grade 3 clinically significant, therapy-related toxicities that do not resolve to grade ≤ 2 within one week
Measured: Days 1, 8, 15, and 52
Percent of participants with diarrhea and oral mucositis and other non-hematologic toxicities
Percent of participants with diarrhea and oral mucositis and other non-hematologic toxicities will be assessed according to CTCAE v.5.0 during the inpatient transplant phase.
Measured: Day 52
Percent of participants with post-transplant period safety
Safety assessed by absence of any grade 4 or higher diarrhea or oral mucositis lasting more than 2 days.
Measured: Day 52
Percent of participants with engraftment failure
Neutrophil engraftment will be defined as the first day of 3 consecutive lab values obtained on different days when the ANC (absolute neutrophil count) is greater than or equal to 0.5 x 109/L (500/μl). Any Engraftment later than 28 days after hematopoietic stem cell infusion will count as engraftment failure.
Measured: Day 52
Percent of participants with safety stopping endpoints
The following study drug-related toxicities, assessed based on CTCAE v.5.0, will count as safety stopping endpoints for this trial:
- non-hematologic toxicity grade 3 or higher that do not resolve to ≤grade 2 within one week occurring in any patient at any time during the study;
- any grade 4 toxicity in two or more patients with any duration in the pre-transplant phase and
- any oral mucositis or diarrhea grade 4 toxicity in two or more patients last more than 2 days in the inpatient transplant phase.
- Neutrophil engraftment failure in more than 2 patients (10% of enrolled patients), and
- any death on trial whether in pre-transplant or post-transplant phase.
Measured: Day 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2021
- Study startSep 2023 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionMar 2024 (estimated)
Why it stopped: The original principal Investigator left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Koen van Besien
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Koen van Besien, Case Comprehensive Cancer Center
- Investigators
- Koen van Besien, MD, PhD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05013437
- Sponsor's protocol ID
- CASE1A20
- Acronym
- AHCT
- Status last verified
- Apr 2024
- First submitted
- 13 Aug 2021
- Last updated
- 2 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) that underlie results in publication
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess Impact of Low Dose Melphalan on Disease Burden Measured by Next Generation Sequencing Before Autologous Hematopoietic Cell Transplant (AHCT) for Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT05013437
- Acronym / sponsor ID
- AHCT / CASE1A20
- Conditions
- Multiple Myeloma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The original principal Investigator left the institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Koen van BesienUniversity, hospital or other
- Study start
- Sep 2023 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Mar 2024 (estimated)
- First posted
- 19 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evomela (Melphalan) | Experimental | Drug: Evomela, Device: Next Generation Sequencing, Drug: Prochlorperazine, Drug: Acetaminophen, Drug: DiphenhydramineParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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)
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvomelaAlso: Melphalan16 mg/m^2 Evomela administered one time via a central line | Drug | Evomela (Melphalan) |
| Next Generation SequencingNext Generation Sequencing | Device | Evomela (Melphalan) |
| Prochlorperazine10mg once intravenous (IV) within 30 minutes before Evomela | Drug | Evomela (Melphalan) |
| Acetaminophen650 mg once orally within 30 minutes before Evomela | Drug | Evomela (Melphalan) |
| Diphenhydramine50 mg once intravenously within 30 minutes before Evomela | Drug | Evomela (Melphalan) |
Primary outcome
Residual myeloma cell number measured by NGS
Time frame: At baseline
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.
Residual myeloma cell number measured by NGS
Time frame: After treatment, day 15
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.
6 secondary outcomes
Toxicity in pre-transplant period assessed according to CTCAE v. 5.0
Time frame: Days 1, 8, 15, and 52
Percent of participants with pre-transplant period safety
Time frame: Days 1, 8, 15, and 52
Percent of participants with diarrhea and oral mucositis and other non-hematologic toxicities
Time frame: Day 52
Percent of participants with post-transplant period safety
Time frame: Day 52
Percent of participants with engraftment failure
Time frame: Day 52
Percent of participants with safety stopping endpoints
Time frame: Day 52
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) that underlie results in publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koen van Besien, MD, PhD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Evomela, Next Generation Sequencing and Prochlorperazine in people with Multiple Myeloma, run by Koen van Besien at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual myeloma cell number measured by NGS (time frame: At baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.