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Trial record 3 of 19 for:    hofmeister

Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant

This study is not yet open for participant recruitment.
Verified October 2017 by Craig Hofmeister, Ohio State University Comprehensive Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03328936
First Posted: November 1, 2017
Last Update Posted: November 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
October 3, 2017
November 1, 2017
November 1, 2017
December 1, 2017
March 31, 2021   (Final data collection date for primary outcome measure)
Complete response proportion [ Time Frame: At 90 days ]
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.
Same as current
No Changes Posted
  • Incidence of melphalan hydrochloride-related toxicities [ Time Frame: Up to 3.5 years ]
    Will assess melphalan-related toxicities (possibly, probably, or definitely related to high dose melphalan) including the incidence of grade 3/4 mucositis, grade 3/4 bacteremia, length of inpatient stay, duration of severe neutropenia (absolute neutrophil count < 500), duration of severe thrombocytopenia (Platelet < 20K), and proportion with tachyarrhythmias (e.g. atrial fibrillation with rapid ventricular rate).
  • Minimal residual disease negative proportions [ Time Frame: Pre-transplant ]
    Will be assessed by standard next generation sequencing.
  • Minimal residual disease negative proportions [ Time Frame: up to 1 year ]
    Will be assessed by standard next generation sequencing.
  • Overall survival [ Time Frame: time from randomization to death, assessed up to 3.5 years ]
    Will be assessed.
  • Progression free survival [ Time Frame: Time from transplant to death, clinical relapse, progressive disease, and death in all treated patients, assessed up to 3.5 years ]
    Will be assessed.
  • Time to biochemical relapse [ Time Frame: Time from start of melphalan hydrochloride until the earliest of the following time points: progressive disease, clinical relapse, or relapse from complete response, assessed up to 3.5 years ]
    Will be assessed.
  • Time to progression [ Time Frame: Time from start of melphalan hydrochloride until the criteria for disease progression are met, assessed up to 3.5 years ]
    Will be assessed.
Same as current
  • Deoxyribonucleic acid (DNA) damage repair [ Time Frame: Up to 3.5 years ]
    Will compare DNA damage repair efficiency in patients that have minimal response to induction and high dose melphalan hydrochloride (partial response or less) compared to those that are sequencing minimal residual disease negative.
  • Half maximal inhibitory concentration (IC50) [ Time Frame: Up to 3.5 years ]
    Will create a multivariate linear regression model that includes each patient?s IC50, DNA repair gene single nucleotide polymorphism (SNP) presence or absence, and revised Multiple Myeloma International Staging System with progression free survival as the outcome.
  • Melphalan hydrochloride pharmacokinetics (PK) parameters [ Time Frame: Within 2 hours prior to start of melphalan hydrochloride infusion and at 5, 30, 45, and 60 minutes, and 3 and 6 hours ]
    Will compare the prediction accuracy of melphalan hydrochloride pharmacokinetics using the test dose versus the current PK model. Test the use of aspects of test dose PK as a covariate in the current high dose melphalan hydrochloride prediction model.
  • p53 messenger ribonucleic acid [ Time Frame: Up to 3.5 years ]
    Will correlate with progression free survival.
  • Phosphorylated TP53 [ Time Frame: Up to 3.5 years ]
    Will correlate with progression free survival.
  • PK/pharmacodynamics (PD) model [ Time Frame: Up to 3.5 years ]
    Will determine the parameter accuracy and precision of the newly integrated PK/PD model for absolute neutrophil count, mucositis, tachyarrhythmias, and disease progression.
  • XRCC1 rs25487 and XRCC3 rs861529 variant alleles [ Time Frame: Up to 3.5 years ]
    Will use Cox survival analysis, measure progression free survival of patients with XRCC1 rs25487 and XRCC3 rs861529 variant alleles compared to wild type.
Same as current
 
Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant
Randomized Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant
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.

PRIMARY OBJECTIVES:

I. Identify whether targeting approximate (approx.) 3- or 5-days of severe neutropenia after exposure to a personalized melphalan hydrochloride (melphalan) dose results in best clinical outcome.

II. Measure melphalan-related toxicities in both 3-day and 5-day arms. III. Measure response per International Myeloma Working Group (IMWG). IV. Record overall survival (OS) and progression free survival (PFS).

SECONDARY OBJECTIVES:

I. To administer a test dose of melphalan and obtain test dose melphalan pharmacokinetics (PK) data from the first 33 patients.

II. Measure drug-induced deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs) treated with melphalan ex vivo post exposure.

III. Measure drug-induced DNA damage in patient myeloma cells treated with melphalan ex vivo.

IV. Assess melphalan-induced DNA damage in treated patients. V. Measure allele and genotype frequencies of variants, as well as gene expression of XRCC1 rs25487 and XRCC3 rs861529.

VI. Additional genetic variants relevant to DNA repair, melphalan transport, and clinical toxicities may be tested as well.

VII. Test cytotoxicity (half maximal inhibitory concentration [IC50]) of patient PBMCs prior to autologous transplant after exposure to melphalan ex vivo.

VIII. Measure p53 and phospho(TP53) in patient PBMCs prior to autologous transplant at baseline and after exposure to melphalan ex vivo.

IX. Incorporate both disease progression and drug-related toxicities into separate models linked to our calculated melphalan area under the curve (AUC) model.

OUTLINE: Patients are randomized into 1 of 2 arms.

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

ARM II: 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.

After completion of study treatment, patients are followed up for 30 days, at 3 months after transplant, and then every 6-12 months.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Hematopoietic Cell Transplantation Recipient
  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Melphalan Hydrochloride
    Given personalized dose IV for predicted 3-day duration of severe neutropenia
    Other Names:
    • Alkeran
    • Alkerana
    • Evomela
  • Drug: Melphalan Hydrochloride
    Given personalized dose IV for predicted 5-day duration of severe neutropenia
    Other Names:
    • Alkeran
    • Alkerana
    • Evomela
  • Other: Pharmacological Study
    Correlative studies
  • Experimental: Arm I (melphalan hydrochloride for 3-day severe neutropenia)
    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.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Drug: Melphalan Hydrochloride
    • Other: Pharmacological Study
  • Experimental: Arm II (melphalan hydrochloride or 5-day severe neutropenia))
    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.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Drug: Melphalan Hydrochloride
    • Other: Pharmacological Study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
100
March 31, 2021
March 31, 2021   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • Females of childbearing potential (FCBP) must not be pregnant as per institutional standard; if no institutional standard exists, then patients must have a negative serum or urine pregnancy test prior to transplant; a 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)

Exclusion Criteria:

  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu
Contact: Nicholas Voss Nicholas.Voss@osumc.edu
United States
 
 
NCT03328936
OSU-17082
NCI-2017-01702 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA016058 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
Ohio State University Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Craig Hofmeister, MD Ohio State University Comprehensive Cancer Center
Ohio State University Comprehensive Cancer Center
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP