Personalized Autologous Transplant for Multiple Myeloma

NCT04483206 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00000449NCI-2020-04920WINSHIP5001-20P30CA138292
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Predicted versus observed total melphalan area under the curve (AUC)

  Will be measured using pharmacokinetic data from the day -3 and day -1 dose.

  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.

  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).

  Up to 90 days post-transplant

Secondary Outcomes (2)

• Overall response rate

  Up to 90 days post transplantation

• Incidence of selected grade 3/4 toxicities at the recommended AUC range

  Up to 60 days post transplantation

Study Arms (1)

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.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Melphalan; Other: Questionnaire Administration

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo ASCT

Also known as: AHSCT, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous

Treatment (Melphalan-based autologous transplant)

Melphalan DRUG

Given IV

Also known as: Alkeran

Treatment (Melphalan-based autologous transplant)

Questionnaire Administration OTHER

Ancillary studies

Treatment (Melphalan-based autologous transplant)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• Gateway for Cancer Research: collaborator

Study Sites (2)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University Illinois Chicago

Chicago, Illinois, 60607, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Stem Cell Transplantation; Melphalan

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)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Craig C Hofmeister, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Craig Hofmeister, MD, MPH

CONTACT

404-778-1900; craig.hofmeister@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 23, 2020
• Study Start: May 20, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)