Multiple MyelomaPhase 1/2NCT00325416
Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.
A Phase 1/2 study testing melphalan, topotecan (TPT) and Autologous Stem Cell Rescue in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this research study is to determine the safest dose of topotecan when given in a high dose before a stem cell transplant; topotecan will be given with melphalan. 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?
- melphalan, topotecan (TPT) and Autologous Stem Cell Rescue
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 177 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2001to 30 Jan 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Multiple Myeloma Criteria = Newly diagnosed with drug sensitive disease (>50% tumor response to standard chemotherapy) and poor prognostic indicators, such as Salmon-Durie stage III, serum b-2-microglobulin >3.0 mg/L, high proliferative fraction or hypodiploidy. Relapsed patients after a response to standard chemotherapy. Patients with primary refractory disease. Patients with non-secretory multiple myeloma are eligible for enrollment on this study. They will be followed for toxicity, survival and molecular endpoint analyses, but will not be followed for response. Patients with plasma cell leukemia, either occurring de novo or arising from existing multiple myeloma, are ineligible for this study.
- Patients greater than or equal to 18 years of age are eligible.
- Patients must have histologically confirmed diagnosis by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute.
- Patients must have undergone a complete psychosocial evaluation and been considered capable of compliance.
- Patients willing and able to receive palifermin (young cohort only)
Who cannot join
- Patients with a diffusing lung capacity oxygenation (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive disease are ineligible.
- Patients with a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance of less than 40 ml/minute. Creatinine clearance can be measured or calculated. Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the discretion of the principal investigator. However, patients on hemodialysis or peritoneal dialysis are ineligible.
- Patients with a total bilirubin greater than 2.0 mg/dL and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
- Patients who have evidence of severe cardiac dysfunction are ineligible. A gated blood pool (MUGA) scan must show an ejection fraction of at least 50%. Patients must be free of major heart disease. Patients are ineligible if they have received a total dose of doxorubicin of greater than 450 mg/m2 (or daunorubicin equivalent) unless the left ventricular ejection fraction by MUGA scan is at least 50%. Patients must not be taking nitroglycerin preparations for angina pectoris or antiarrhythmic drugs for major ventricular dysrhythmias. Patients with essential hypertension controlled with medications are eligible for study. Any patient with congenital or acquired heart disease or cardiac arrhythmias will have a cardiology consult and evaluation.
- Patients with active infections are ineligible.
- Patients who are HIV antibody positive are ineligible.
Show all 12Show fewer
- Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible.
- Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction are ineligible.
- Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of > or = 2 are ineligible. Patients with ECOG performance status 2 to 3 secondary to bone pain may be enrolled at the discretion of the institutional investigator. Patients with ECOG performance status 2 to 3 secondary to a potentially reversible disease-related problem may be enrolled at the discretion of the institutional investigator.
- Patients who are pregnant or lactating are ineligible.
- Patients with any previous malignancy other than non-melanoma skin cancer are ineligible, unless the patient is without evidence of disease > or = 5 years after the treatment for the cancer was completed.
- Patients previously treated with topotecan or any other topoisomerase I inhibitor.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: A Study of Intensive-Dose Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.
The purpose of this research study is to determine the safest dose of topotecan when given in a high dose before a stem cell transplant; topotecan will be given with melphalan.
Read the detailed description
The stem cells being transplanted are cells found in the bone marrow and blood that are responsible for making red blood cells, white blood cells, and platelets. The stem cells are collected by a process called leukapheresis and will be frozen for later use. After receiving the chemotherapy drugs, the stem cells will be thawed and given like a blood transfusion. This is called autologous stem cell transplant or rescue. The study doctors will be measuring how well the disease responds to the drugs as well as any side effects to the drugs. During the course of this study, blood and bone marrow samples will be obtained to measure levels of the chemotherapy drugs as well as levels of certain enzymes (proteins).
The staff of the Blood and Marrow Transplant program will continue to collect information about the participant's disease and its treatment for the rest of their life.
- Conditions
- Multiple Myeloma
- Being tested
- melphalan, topotecan (TPT), Autologous Stem Cell Rescue
- Keywords
- melphalan, topotecan, topoisomerase, bone marrow transplant, drug sequence
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
melphalanDrug
Also called Alkeran®
(Days -4,-3,-2) 50 mg/m^2/day IV over 30 minutes (total dose 150 mg/m^2)
topotecan (TPT)Drug
Also called Hycamtin®
Phase I Dose Escalation: Level 1 - 20 mg/m^2; Level 2 - 30 mg/m^2; Level 4 - 54 mg/m^2; Level 5 - 72 mg/m^2; Level 6 - 96 mg/m^2; Level 7 - 127.8 mg/m^2; Level 8 - 170.1 mg/m^2
Phase II: Treatment at maximum tolerated dose (MTD)
Autologous Stem Cell RescueProcedure or surgery
Also called Bone Marrow Transplant, Stem Cell Transplant
Day 0
| Study group | Role | What they receive |
|---|---|---|
| Age Group A - Melphalan and Topotecan plus Stem Cell Rescue | Experimental | Participants 18 - 60 years of age. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant. Receives: Drug: melphalan; Drug: topotecan (TPT); Procedure: Autologous Stem Cell Rescue |
| Age Group B - Melphalan and Topotecan plus Stem Cell Rescue | Active comparator | Participants 61 years of age or older. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant. Receives: Drug: melphalan; Drug: topotecan (TPT); Procedure: Autologous Stem Cell Rescue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I - Maximum Tolerated Dose (MTD) Level
MTD of topotecan in multiple myeloma patients receiving autologous transplant when give with melphalan 150 mg/m^2 for three days. Two parallel dose escalations were used, one each for young (18-60 years of age) and elderly patients (> 61 years of age). Elderly patients began a dose level once it had been found to be safe for the young cohort. The purpose of this approach was to expand the access of this trial to elderly patients while ensuring safety.
Phase I Dose Escalation: Level 1 - 20 mg/m^2; Level 2 - 30 mg/m^2; Level 4 - 54 mg/m^2; Level 5 - 72 mg/m^2; Level 6 - 96 mg/m^2; Level 7 - 127.8 mg/m^2; Level 8 - 170.1 mg/m^2
Measured: Phase I - 5 years, 2 months
Phase II Participants - Overall Response Rate
Re-evaluation of participants who had responsive disease prior to transplant. All changes in monoclonal protein and immunoglobulins will be referenced to those levels obtained immediately prior to cyclophosphamide priming chemotherapy. Complete Response (CR): A CR will be defined as the disappearance of the monoclonal protein by immunofixation studies of serum and urine (100x concentrate) and less than or equal to 5% plasma cells in a bone marrow aspirate. Partial Response (PR): 50% - 74% decrease in the measurable monoclonal protein (M-component from an SPEP and/or UPEP with immunofixation).
Measured: Phase II - Phase start at 62 months up to 120 months
Secondary outcomes (2)
Phase II Event Free Survival (EFS)
Time to treatment failure, which is defined as the time from day 0 to the time of progressive disease. Progressive disease is defined by unequivocal objective evidence and constitutes any of the following: 1). an increase in the total amount of monoclonal protein (M-component from Serum Protein Electrophoresis (SPEP) and/or Urine Protein Electrophoresis (UPEP) with immunofixation) by more than 100% from the lowest level of serum myeloma protein seen after high-dose chemotherapy by serum protein electrophoresis; 2). an increase in the total amount of monoclonal protein above the remission level of the myeloma peak (i.e., an increase of >25% above the lowest level in a 24 hour urine or serum protein; 3). the reappearance of the M-protein if the patient had entered a CR: 4). definite increase in the size (> 1 cm) or number of lytic bone lesions. Compression fractures do not constitute a relapse.
Measured: Phase II - Phase start at 62 months up to 120 months
Phase II Overall Survival (OS)
Time from start of treatment until death from any cause.
Measured: Phase II - Phase start at 62 months up to 120 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2006 (estimated)
- Study start19 Nov 2001
- Primary completion15 Jul 2013
- Study completion30 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Daniel M Sullivan, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00325416
- Sponsor's protocol ID
- MCC-12733
- Status last verified
- Feb 2018
- First submitted
- 11 May 2006
- Last updated
- 14 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Intensive-Dose Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.
- ClinicalTrials.gov ID
- NCT00325416
- Acronym / sponsor ID
- MCC-12733
- Conditions
- Multiple Myeloma
- Keywords
- melphalan, topotecan, topoisomerase, bone marrow transplant, drug sequence
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, National Cancer Institute (NCI)
- Study start
- 19 Nov 2001 (actual)
- Primary completion
- 15 Jul 2013 (actual)
- Study completion
- 30 Jan 2018 (actual)
- First posted
- 12 May 2006 (estimated)
- Results
- Posted 23 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine the safest dose of topotecan when given in a high dose before a stem cell transplant; topotecan will be given with melphalan.
Detailed description
The stem cells being transplanted are cells found in the bone marrow and blood that are responsible for making red blood cells, white blood cells, and platelets. The stem cells are collected by a process called leukapheresis and will be frozen for later use. After receiving the chemotherapy drugs, the stem cells will be thawed and given like a blood transfusion. This is called autologous stem cell transplant or rescue. The study doctors will be measuring how well the disease responds to the drugs as well as any side effects to the drugs. During the course of this study, blood and bone marrow samples will be obtained to measure levels of the chemotherapy drugs as well as levels of certain enzymes (proteins).
The staff of the Blood and Marrow Transplant program will continue to collect information about the participant's disease and its treatment for the rest of their life.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Age Group A - Melphalan and Topotecan plus Stem Cell Rescue | Experimental | Drug: melphalan, Drug: topotecan (TPT), Procedure: Autologous Stem Cell RescueParticipants 18 - 60 years of age. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant. |
| Age Group B - Melphalan and Topotecan plus Stem Cell Rescue | Active comparator | Drug: melphalan, Drug: topotecan (TPT), Procedure: Autologous Stem Cell RescueParticipants 61 years of age or older. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Multiple Myeloma Criteria = Newly diagnosed with drug sensitive disease (>50% tumor response to standard chemotherapy) and poor prognostic indicators, such as Salmon-Durie stage III, serum b-2-microglobulin >3.0 mg/L, high proliferative fraction or hypodiploidy. Relapsed patients after a response to standard chemotherapy. Patients with primary refractory disease. Patients with non-secretory multiple myeloma are eligible for enrollment on this study. They will be followed for toxicity, survival and molecular endpoint analyses, but will not be followed for response. Patients with plasma cell leukemia, either occurring de novo or arising from existing multiple myeloma, are ineligible for this study.
- Patients greater than or equal to 18 years of age are eligible.
- Patients must have histologically confirmed diagnosis by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute.
- Patients must have undergone a complete psychosocial evaluation and been considered capable of compliance.
- Patients willing and able to receive palifermin (young cohort only)
Key exclusion criteria (12 listed)
- Patients with a diffusing lung capacity oxygenation (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive disease are ineligible.
- Patients with a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance of less than 40 ml/minute. Creatinine clearance can be measured or calculated. Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the discretion of the principal investigator. However, patients on hemodialysis or peritoneal dialysis are ineligible.
- Patients with a total bilirubin greater than 2.0 mg/dL and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
- Patients who have evidence of severe cardiac dysfunction are ineligible. A gated blood pool (MUGA) scan must show an ejection fraction of at least 50%. Patients must be free of major heart disease. Patients are ineligible if they have received a total dose of doxorubicin of greater than 450 mg/m2 (or daunorubicin equivalent) unless the left ventricular ejection fraction by MUGA scan is at least 50%. Patients must not be taking nitroglycerin preparations for angina pectoris or antiarrhythmic drugs for major ventricular dysrhythmias. Patients with essential hypertension controlled with medications are eligible for study. Any patient with congenital or acquired heart disease or cardiac arrhythmias will have a cardiology consult and evaluation.
- Patients with active infections are ineligible.
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 |
|---|---|---|
| melphalanAlso: Alkeran®(Days -4,-3,-2) 50 mg/m^2/day IV over 30 minutes (total dose 150 mg/m^2) | Drug | Age Group A - Melphalan and Topotecan plus Stem Cell Rescue, Age Group B - Melphalan and Topotecan plus Stem Cell Rescue |
| topotecan (TPT)Also: Hycamtin®Phase I Dose Escalation: Level 1 - 20 mg/m^2; Level 2 - 30 mg/m^2; Level 4 - 54 mg/m^2; Level 5 - 72 mg/m^2; Level 6 - 96 mg/m^2; Level 7 - 127.8 mg/m^2; Level 8 - 170.1 mg/m^2 Phase II: Treatment at maximum tolerated dose (MTD) | Drug | Age Group A - Melphalan and Topotecan plus Stem Cell Rescue, Age Group B - Melphalan and Topotecan plus Stem Cell Rescue |
| Autologous Stem Cell RescueAlso: Bone Marrow Transplant, Stem Cell TransplantDay 0 | Procedure or surgery | Age Group A - Melphalan and Topotecan plus Stem Cell Rescue, Age Group B - Melphalan and Topotecan plus Stem Cell Rescue |
Primary outcome
Phase I - Maximum Tolerated Dose (MTD) Level
Time frame: Phase I - 5 years, 2 months
MTD of topotecan in multiple myeloma patients receiving autologous transplant when give with melphalan 150 mg/m^2 for three days. Two parallel dose escalations were used, one each for young (18-60 years of age) and elderly patients (> 61 years of age). Elderly patients began a dose level once it had been found to be safe for the young cohort. The purpose of this approach was to expand the access of this trial to elderly patients while ensuring safety. Phase I Dose Escalation: Level 1 - 20 mg/m^2; Level 2 - 30 mg/m^2; Level 4 - 54 mg/m^2; Level 5 - 72 mg/m^2; Level 6 - 96 mg/m^2; Level 7 - 127.8 mg/m^2; Level 8 - 170.1 mg/m^2
Phase II Participants - Overall Response Rate
Time frame: Phase II - Phase start at 62 months up to 120 months
Re-evaluation of participants who had responsive disease prior to transplant. All changes in monoclonal protein and immunoglobulins will be referenced to those levels obtained immediately prior to cyclophosphamide priming chemotherapy. Complete Response (CR): A CR will be defined as the disappearance of the monoclonal protein by immunofixation studies of serum and urine (100x concentrate) and less than or equal to 5% plasma cells in a bone marrow aspirate. Partial Response (PR): 50% - 74% decrease in the measurable monoclonal protein (M-component from an SPEP and/or UPEP with immunofixation).
2 secondary outcomes
Phase II Event Free Survival (EFS)
Time frame: Phase II - Phase start at 62 months up to 120 months
Phase II Overall Survival (OS)
Time frame: Phase II - Phase start at 62 months up to 120 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- H. Lee Moffitt Cancer Center \& Research InstituteLink 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.
Daniel M Sullivan, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing melphalan, topotecan (TPT) and Autologous Stem Cell Rescue in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute 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 5 inclusion and 12 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: finished, as of the sponsor's last update on 14 Mar 2018. 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 23 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase I - Maximum Tolerated Dose (MTD) Level (time frame: Phase I - 5 years, 2 months). The study lists 2 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 14 Mar 2018.