Acute LeukemiaPhase 1NCT01314599
Clinical Study of PM01183 in Patients With Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome
A Phase 1 study testing PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion in people with Acute Leukemia, run by PharmaMar at 2 sites in United States.
Trial summary
Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Leukemia
- What is being tested?
- PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2011to Jul 2015
- Phase
- Phase 1
- 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
- Voluntarily signed and dated written informed consent
- Age ≥ 18 years.
- Patients must have a previous cytological or histological diagnosis of:
- Relapsed or primary refractory non-M3 acute myeloid leukemia (AML) by the World Health Organization (WHO) criteria (irrespective of the number of prior regimens), either de novo or secondary [i.e., secondary to myelodysplastic syndromes (MDS), myeloproliferative neoplasms or previous chemotherapy for another condition].
- Untreated AML in patients ≥ 65 years of age, if patients are not candidates for standard induction chemotherapy or have poor risk AML (i.e., secondary AML or AML with adverse cytogenetics or complex karyotype).
- Accelerated or blastic phase chronic myeloid leukemia (CML, with progressive disease despite treatment with BCR-ABL kinase inhibitors), or chronic myelomonocytic leukemia (CMML).
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- Relapsed or refractory acute lymphoblastic leukemia (ALL) by WHO criteria.
- Patients must have the following laboratory values prior to the start of treatment:
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) range of values, unless due to elevated indirect bilirubin (e.g.,Gilbert's syndrome or hemolysis).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
- Alkaline phosphatase (AP) ≤ 2.5 x ULN.
- Albumin ≥ 2.5 g/dl.
- Calculated creatinine clearance (CrCl) ≥ 30 ml/min (using Cockcroft and Gault's formula).
- Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- Negative pregnancy test for women of childbearing potential.
Who cannot join
- Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods throughout the treatment period and for six months after discontinuation of treatment.
- Patients who plan to undergo allogeneic BM transplantation within four weeks.
- Other relevant diseases or adverse clinical conditions:
- History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
- Symptomatic or unstable cardiac arrhythmias, and/or prolonged QT-QTc grade ≥ 2.
- History of significant neurological or psychiatric disorders that may affect the patient's compliance with the protocol assessments.
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- Active uncontrolled infection.
- Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 x ULN in two different determinations performed one week apart).
- Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
- Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
- Hematopoietic allogeneic stem cell transplantation within the last four months and/or active graft versus host disease, or prior autologous transplantation within the last four weeks.
- Patients known to be human immunodeficiency virus (HIV) positive.
- Cytotoxic chemotherapy within the last two weeks; radiation therapy within the last two weeks; biologic agents, including hematopoietic growth factors, within the last week; hydroxyurea, imatinib, corticosteroids and arsenic trioxide should be discontinued at least 24 hours prior to first study drug administration.
- Treatment with any investigational product in the ≤ 5 half-lives period prior to inclusion in the study, or 30 days after therapy (in case of unknown half-life), unless evidence of rapid proliferating disease and upon discussion with the Sponsor.
- Known hypersensitivity to any of the components of the drug product (DP).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Study site
Houston, Texas, 77030
Study site
Rochester, Minnesota, 55905
About this study
Official title: Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of Lurbinectedin (PM01183) in Patients With Advanced Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome.
Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183.
Read the detailed description
Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 administered as 1-hour intravenous (i.v.) infusion on three consecutive days (Days 1-3) to patients with advanced acute leukemia and to assess the safety profile and tolerability, to obtain preliminary information on the efficacy and to characterize the pharmacokinetics (PK) and pharmacogenomic (PGx) profile of PM01183.
- Conditions
- Acute Leukemia
- Being tested
- PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion
- Keywords
- Leukemia, lurbinectedin, PM01183, Pharma Mar, Acute Leukemia in Relapse and Primary Refractory
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusionDrug
PM01183 Drug Product will be provided as a lyophilized powder for concentrate for solution for infusion with a strength of 1.0 mg/vial and 4.0 mg/vial.
Before use, the vials will be reconstituted with 2 ml or 8 ml of sterile water for injection to give a solution containing 0.5 mg/ml of PM01183.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | PM01183 will be administered i.v. as a 1-hour infusion through a pump device at escalating doses according to the respective dose level, on Days 1 and 8 of each treatment phase. Receives: Drug: PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of PM01183 in patients with advanced acute leukemia.
The recommended dose (RD) will be the immediate lower DL below the MTD (maximum tolerated dose)with less than 1/3 of the first 6 evaluable patients experiencing DLT (dose limiting toxicity)during the induction, provided the RD is ≥ dose level 2. If the RD is determined at dose level 1, no further expansion will be done, and the study will be terminated.
Measured: Up to 30 months
Secondary outcomes (3)
Antileukemic activity
Activity will be defined according to the International Working Group (IWG) criteria.
Measured: After induction/reinduction and every 4 weeks after treatment discontinuation; up to 30 months
Pharmacogenomic (PGx) profile of PM01183 in patients with advanced acute leukemia.
Identification of potential biomarkers of response to PM01183
Measured: Between day -24 to day 1
Pharmacokinetics (PK) of PM01183 in patients with advanced acute leukemia
The PK will be elucidated using standard non-compartmental methods. The following parameters will be calculated: maximum drug concentration (Cmax), area under the curve (AUC), volume of distribution based on the terminal half-life (Vz), volume of distribution at steady state (Vss), clearance (CL) and half-life (t1/2)
Measured: Days 1 to 8 of induction and day 1 of next phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2011 (estimated)
- Study startMay 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01314599
- Sponsor's protocol ID
- PM1183-A-002-10
- Status last verified
- Jul 2015
- First submitted
- 9 Mar 2011
- Last updated
- 5 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of Lurbinectedin (PM01183) in Patients With Advanced Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome.
- ClinicalTrials.gov ID
- NCT01314599
- Acronym / sponsor ID
- PM1183-A-002-10
- Conditions
- Acute Leukemia
- Keywords
- Leukemia, lurbinectedin, PM01183, Pharma Mar, Acute Leukemia in Relapse and Primary Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- PharmaMarIndustry (pharma, biotech, devices)
- Study start
- May 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 14 Mar 2011 (estimated)
- 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.
Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183.
Detailed description
Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of PM01183 in Patients with Advanced Acute Leukemia to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 administered as 1-hour intravenous (i.v.) infusion on three consecutive days (Days 1-3) to patients with advanced acute leukemia and to assess the safety profile and tolerability, to obtain preliminary information on the efficacy and to characterize the pharmacokinetics (PK) and pharmacogenomic (PGx) profile of PM01183.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusionPM01183 will be administered i.v. as a 1-hour infusion through a pump device at escalating doses according to the respective dose level, on Days 1 and 8 of each treatment phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Voluntarily signed and dated written informed consent
- Age ≥ 18 years.
- Patients must have a previous cytological or histological diagnosis of:
- Patients must have the following laboratory values prior to the start of treatment:
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
Key exclusion criteria (15 listed)
- Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods throughout the treatment period and for six months after discontinuation of treatment.
- Patients who plan to undergo allogeneic BM transplantation within four weeks.
- Other relevant diseases or adverse clinical conditions:
- Hematopoietic allogeneic stem cell transplantation within the last four months and/or active graft versus host disease, or prior autologous transplantation within the last four weeks.
- Patients known to be human immunodeficiency virus (HIV) positive.
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 |
|---|---|---|
| PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusionPM01183 Drug Product will be provided as a lyophilized powder for concentrate for solution for infusion with a strength of 1.0 mg/vial and 4.0 mg/vial. Before use, the vials will be reconstituted with 2 ml or 8 ml of sterile water for injection to give a solution containing 0.5 mg/ml of PM01183. | Drug | Arm 1 |
Primary outcome
Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of PM01183 in patients with advanced acute leukemia.
Time frame: Up to 30 months
The recommended dose (RD) will be the immediate lower DL below the MTD (maximum tolerated dose)with less than 1/3 of the first 6 evaluable patients experiencing DLT (dose limiting toxicity)during the induction, provided the RD is ≥ dose level 2. If the RD is determined at dose level 1, no further expansion will be done, and the study will be terminated.
3 secondary outcomes
Antileukemic activity
Time frame: After induction/reinduction and every 4 weeks after treatment discontinuation; up to 30 months
Pharmacogenomic (PGx) profile of PM01183 in patients with advanced acute leukemia.
Time frame: Between day -24 to day 1
Pharmacokinetics (PK) of PM01183 in patients with advanced acute leukemia
Time frame: Days 1 to 8 of induction and day 1 of next phase
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion in people with Acute Leukemia, run by PharmaMar at 2 sites 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 15 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 5 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of PM01183 in patients with advanced acute leukemia. (time frame: Up to 30 months). 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 5 Nov 2015.