Hematopoietic Cell Transplantation RecipientPhase 2NCT03328936
Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant
A Phase 2 study testing Laboratory Biomarker Analysis, Melphalan Hydrochloride and Pharmacological Study in people with Hematopoietic Cell Transplantation Recipient and Recurrent Plasma Cell Myeloma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic Cell Transplantation Recipient, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Laboratory Biomarker Analysis, Melphalan Hydrochloride and Pharmacological Study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2018to 31 Mar 2021
- Phase
- Phase 2
- 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
- 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
Show all 16Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Hematopoietic Cell Transplantation Recipient, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Being tested
- Laboratory Biomarker Analysis, Melphalan Hydrochloride, Pharmacological Study
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Melphalan HydrochlorideDrug
Also called Alkeran, Alkerana, Evomela
Given personalized dose IV for predicted 3-day duration of severe neutropenia
Melphalan HydrochlorideDrug
Also called Alkeran, Alkerana, Evomela
Given personalized dose IV for predicted 5-day duration of severe neutropenia
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 90 days
Secondary outcomes (7)
Incidence of melphalan hydrochloride-related toxicities
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).
Measured: Up to 3.5 years
Minimal residual disease negative proportions
Will be assessed by standard next generation sequencing.
Measured: Pre-transplant
Minimal residual disease negative proportions
Will be assessed by standard next generation sequencing.
Measured: up to 1 year
Overall survival
Will be assessed.
Measured: time from randomization to death, assessed up to 3.5 years
Progression free survival
Will be assessed.
Measured: Time from transplant to death, clinical relapse, progressive disease, and death in all treated patients, assessed up to 3.5 years
Time to biochemical relapse
Will be assessed.
Measured: 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
Time to progression
Will be assessed.
Measured: Time from start of melphalan hydrochloride until the criteria for disease progression are met, assessed up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start1 Sep 2018 (estimated)
- Primary completion31 Mar 2021 (estimated)
- Study completion31 Mar 2021 (estimated)
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic Cell Transplantation RecipientStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ashley Rosko, Ohio State University Comprehensive Cancer Center
- Investigators
- Ashley Rosko, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03328936
- Sponsor's protocol ID
- OSU-17082
- Other IDs
- NCI-2017-01702, P30CA016058
- Status last verified
- Feb 2020
- First submitted
- 3 Oct 2017
- Last updated
- 21 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant
- ClinicalTrials.gov ID
- NCT03328936
- Acronym / sponsor ID
- OSU-17082
- Conditions
- Hematopoietic Cell Transplantation Recipient, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Sep 2018 (estimated)
- Primary completion
- 31 Mar 2021 (estimated)
- Study completion
- 31 Mar 2021 (estimated)
- First posted
- 1 Nov 2017 (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 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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (melphalan hydrochloride for 3-day severe neutropenia) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Melphalan Hydrochloride, Other: Pharmacological StudyPatients 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. |
| Arm II (melphalan hydrochloride or 5-day severe neutropenia)) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Melphalan Hydrochloride, Other: Pharmacological StudyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (melphalan hydrochloride for 3-day severe neutropenia), Arm II (melphalan hydrochloride or 5-day severe neutropenia)) |
| Melphalan HydrochlorideAlso: Alkeran, Alkerana, EvomelaGiven personalized dose IV for predicted 3-day duration of severe neutropenia | Drug | Arm I (melphalan hydrochloride for 3-day severe neutropenia) |
| Melphalan HydrochlorideAlso: Alkeran, Alkerana, EvomelaGiven personalized dose IV for predicted 5-day duration of severe neutropenia | Drug | Arm II (melphalan hydrochloride or 5-day severe neutropenia)) |
| Pharmacological StudyCorrelative studies | Other | Arm I (melphalan hydrochloride for 3-day severe neutropenia), Arm II (melphalan hydrochloride or 5-day severe neutropenia)) |
Primary outcome
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.
7 secondary outcomes
Incidence of melphalan hydrochloride-related toxicities
Time frame: Up to 3.5 years
Minimal residual disease negative proportions
Time frame: Pre-transplant
Minimal residual disease negative proportions
Time frame: up to 1 year
Overall survival
Time frame: time from randomization to death, assessed up to 3.5 years
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
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
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
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 21 Feb 2020.
- The JameslineLink provided by the sponsor.
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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.
Ashley Rosko, MD principal investigator
Ohio State University 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 Phase 2 study testing Laboratory Biomarker Analysis, Melphalan Hydrochloride and Pharmacological Study in people with Hematopoietic Cell Transplantation Recipient and Recurrent Plasma Cell Myeloma, run by Ohio State University Comprehensive Cancer Center 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 16 inclusion and 5 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 21 Feb 2020. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Complete response proportion (time frame: At 90 days). 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 21 Feb 2020.