Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant

NCT03328936 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: OSU-17082NCI-2017-01702P30CA016058
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies the side effects and how well melphalan hydrochloride works in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as melphalan hydrochloride, 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.

Conditions

Hematopoietic Cell Transplantation Recipient; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Complete response proportion

  Complete response will be defined as complete response + stringent complete response according to the International Myeloma Working Group Uniform response criterion. Will be calculated with an exact 95% confidence interval, both within arms and across arms.

  At 90 days

Secondary Outcomes (7)

• Incidence of melphalan hydrochloride-related toxicities

  Up to 3.5 years

• Minimal residual disease negative proportions

  Pre-transplant

• Minimal residual disease negative proportions

  up to 1 year

• Overall survival

  time from randomization to death, assessed up to 3.5 years

• Progression free survival

  Time from transplant to death, clinical relapse, progressive disease, and death in all treated patients, assessed up to 3.5 years

Other Outcomes (7)

• Deoxyribonucleic acid (DNA) damage repair

  Up to 3.5 years

• Half maximal inhibitory concentration (IC50)

  Up to 3.5 years

• Melphalan hydrochloride pharmacokinetics (PK) parameters

  Within 2 hours prior to start of melphalan hydrochloride infusion and at 5, 30, 45, and 60 minutes, and 3 and 6 hours

Study Arms (2)

Arm I (melphalan hydrochloride for 3-day severe neutropenia)

EXPERIMENTAL

Patients receive personalized dose of melphalan hydrochloride IV on day -2 for for predicted 3-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.

Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Other: Pharmacological Study

Arm II (melphalan hydrochloride or 5-day severe neutropenia))

EXPERIMENTAL

Patients receive personalized dose of melphalan hydrochloride IV on day -2 for predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.

Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (melphalan hydrochloride for 3-day severe neutropenia); Arm II (melphalan hydrochloride or 5-day severe neutropenia))

Melphalan Hydrochloride DRUG

Given personalized dose IV for predicted 3-day duration of severe neutropenia

Also known as: Alkeran, Alkerana, Evomela

Arm I (melphalan hydrochloride for 3-day severe neutropenia)

Pharmacological Study OTHER

Correlative studies

Arm I (melphalan hydrochloride for 3-day severe neutropenia); Arm II (melphalan hydrochloride or 5-day severe neutropenia))

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 relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria for multiple myeloma; patients with AL amyloidosis and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) are excluded; measurable disease is not required
• Patient undergoing autologous transplant as part of first line therapy
• All races and ethnic groups are eligible for this study
• Patients must also have an adequate autologous graft as defined as a cryopreserved peripheral blood stem cell (PBSC) graft containing \> 2 x 10\^6 CD34+ cells/kg patient weight
• 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
• Absolute neutrophil count (ANC) \> 1000/uL
• Platelet count \> 50,000
• Transfusion independent
• Total bilirubin \< 1.5 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x the institutional upper limit of normal
• Left ventricular ejection fraction \>= 40%
• Carbon monoxide diffusing capability (DLCO) \> 50% predicted
• Forced expiratory volume in 1 second (FEV1) \> 50% predicted
• Forced vital capacity (FVC) \> 50% predicted
• Ability to understand and willingness to sign a written informed consent document

You may not qualify if:

• Patients who are receiving any other anti-myeloma investigational agents
• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued
• Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to \< 1 year, or confound data interpretation
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

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)

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

• Ashley Rosko, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: November 1, 2017
• Study Start: September 1, 2018
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: February 21, 2020

Record last verified: 2020-02

Locations

US (1)