Multiple MyelomaPhase 1NCT04483206
Personalized Autologous Transplant for Multiple Myeloma
A Phase 1 study testing Autologous Hematopoietic Stem Cell Transplantation, Melphalan and Questionnaire Administration in people with Multiple Myeloma, run by Emory University at 2 sites in United States.
Trial summary
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… 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?
- Autologous Hematopoietic Stem Cell Transplantation, Melphalan and Questionnaire Administration
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 May 2021to 31 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- 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
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- 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. 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)
- The patient must be willing to comply with fertility requirements
- 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
Who cannot join
- Patients known to meet criteria for progressive disease or clinical relapse between screening and planned melphalan infusion day -3
- Subject has any of the following cardiac abnormalities
- History of clinically significant cardiovascular disease with New York Heart Association class III or IV congestive heart failure or
- Severe non-ischemic cardiomyopathy or
- Myocardial infarction within the previous 6 months prior to starting study treatment
- Unstable or poorly controlled angina
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- Uncontrolled severe hypertension
- Clinically/hemodynamically significant arrythmias
- Severe uncontrolled cardiac arrhythmias (grade 3 or higher) or
- Clinically significant electrocardiogram (ECG) abnormalities includingcorrected QT interval (QTc) > 480 msec
- Human 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.
- Seropositive 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
- Seropositive 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
- Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS) syndrome, amyloid light-chain (AL) amyloidosis, and Waldenstrom macroglobulinemia
- Concurrent 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
- Known 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
- Pregnant 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Loizos C. Nikolaou, 404-778-8658, loizos.nikolaou@emory.edu
Craig C Hofmeister, MD, MPH
- Not yet recruiting
University Illinois Chicago
Chicago, Illinois, 60607
Karen Sweiss, PharmD, 312-996-0875, KSweis2@UIC.EDU
About this study
Official title: Phase 1 of Exposure Targeted Melphalan Dosing
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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 CMMCs numbers obtained with CELLSEARCH with 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.
- Conditions
- Multiple Myeloma
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, Melphalan, Questionnaire Administration
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called AHSCT, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous
Undergo ASCT
MelphalanDrug
Also called Alkeran
Given IV
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Melphalan-based autologous transplant) | Experimental | Patients receive high dose (100 mg/m2) melphalan IV over 30 minutes on day -3 and PK-directed melphalan IV over 30 minutes on day -1 to achieve set cumulative melphalan exposure levels. Patients then undergo stem cell infusion on day 0. Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Melphalan; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Predicted versus observed total melphalan area under the curve (AUC)
Will be measured using pharmacokinetic data from the day -3 and day -1 dose.
Measured: At Days -3 and -1
Incidence of exposure limiting toxicity
Will measure proportion of patients with clinically significant mucositis, tachyarrhythmia, and delayed engraftment. Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) guidelines.
Measured: During the first 30-days of treatment
Minimal residual disease (MRD) negativity post-transplant
MRD status will be determined per International Myeloma Working Group (IMWG) criteria using next generation sequencing in patients with suspected complete response (CR).
Measured: Up to 90 days post-transplant
Secondary outcomes (2)
Overall response rate
The number and percentage of subjects experiencing objective response will be descriptively summarized overall and by cohort. Responders will be defined as those that achieve best response of partial response (PR) or better defined according to the IMWG Uniform response criterion. CR rate will be calculated with an exact 95% confidence interval, both within cohorts but not between cohorts.
Measured: Up to 90 days post transplantation
Incidence of selected grade 3/4 toxicities at the recommended AUC range
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Adverse events will be summarized and described within each cohort. They will initially be reviewed regardless of attribution, but also whether they are possibly, probably, or definitely related to treatment. In addition, will review all adverse event data that are graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe adverse events or toxicities will be described. Will assess the proportion of patients who experience grade 3 or higher non-hematologic toxicity. To assess tolerability, will also capture the proportion of patients who go off treatment due to adverse events.
Measured: Up to 60 days post transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2020
- Study start20 May 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
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.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Gateway for Cancer Research
- Responsible party
- Principal investigator, Craig Hofmeister, Emory University
- Investigators
- Craig C Hofmeister, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04483206
- Sponsor's protocol ID
- STUDY00000449
- Other IDs
- NCI-2020-04920, WINSHIP5001-20, P30CA138292
- Status last verified
- Jun 2026
- First submitted
- 20 Jul 2020
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 of Exposure Targeted Melphalan Dosing
- ClinicalTrials.gov ID
- NCT04483206
- Acronym / sponsor ID
- STUDY00000449
- Conditions
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Gateway for Cancer Research
- Study start
- 20 May 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 23 Jul 2020 (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.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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 CMMCs numbers obtained with CELLSEARCH with 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Melphalan-based autologous transplant) | Experimental | Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: Melphalan, Other: Questionnaire AdministrationPatients receive high dose (100 mg/m2) melphalan IV over 30 minutes on day -3 and PK-directed melphalan IV over 30 minutes on day -1 to achieve set cumulative melphalan exposure levels. Patients then undergo stem cell infusion on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
- 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)
Key exclusion criteria (17 listed)
- Patients known to meet criteria for progressive disease or clinical relapse between screening and planned melphalan infusion day -3
- Subject has any of the following cardiac abnormalities
- Human 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.
- Seropositive 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
- Seropositive 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
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 |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAlso: AHSCT, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplantation, Stem Cell Transplantation, AutologousUndergo ASCT | Procedure or surgery | Treatment (Melphalan-based autologous transplant) |
| MelphalanAlso: AlkeranGiven IV | Drug | Treatment (Melphalan-based autologous transplant) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (Melphalan-based autologous transplant) |
Primary outcome
Predicted versus observed total melphalan area under the curve (AUC)
Time frame: At Days -3 and -1
Will be measured using pharmacokinetic data from the day -3 and day -1 dose.
Incidence of exposure limiting toxicity
Time frame: During the first 30-days of treatment
Will measure proportion of patients with clinically significant mucositis, tachyarrhythmia, and delayed engraftment. Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) guidelines.
Minimal residual disease (MRD) negativity post-transplant
Time frame: Up to 90 days post-transplant
MRD status will be determined per International Myeloma Working Group (IMWG) criteria using next generation sequencing in patients with suspected complete response (CR).
2 secondary outcomes
Overall response rate
Time frame: Up to 90 days post transplantation
Incidence of selected grade 3/4 toxicities at the recommended AUC range
Time frame: Up to 60 days post transplantation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Individual participant dataSharing planned: No
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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.
Craig C Hofmeister, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous Hematopoietic Stem Cell Transplantation, Melphalan and Questionnaire Administration in people with Multiple Myeloma, run by Emory University at 2 sites 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 17 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Craig Hofmeister, MD, MPH (404-778-1900, craig.hofmeister@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Predicted versus observed total melphalan area under the curve (AUC) (time frame: At Days -3 and -1). The study lists 3 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 15 Jun 2026; AzTrials last refreshed its copy on 3 Nov 2026.