Adult Acute Erythroid Leukemia (M6)Phase 2NCT02019069
CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
A Phase 2 study testing liposomal cytarabine-daunorubicin CPX-351 in people with Adult Acute Erythroid Leukemia (M6) and Adult Acute Megakaryoblastic Leukemia (M7), run by Rondeep Brar at 1 site in United States.
Trial summary
This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
- What is being tested?
- liposomal cytarabine-daunorubicin CPX-351
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Feb 2014to 18 Dec 2017
- Phase
- Phase 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and voluntarily give informed consent
- Age ≥ 60
- Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and high risk MDS by IPSS) along with one of the following:
- Patients with de novo or secondary MDS with progression/refractoriness after HMA treatment who have not transformed to AML
- Patients with MDS and prior HMA treatment for MDS who transform to AML
- Patients with AML who are refractory/relapsed after HMA therapy for their AML are eligible
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- Life expectancy > 1 month
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Able to adhere to the study visit schedule and other protocol requirements
- Laboratory values fulfilling the following:
- Serum creatinine < 2.0 mg/dL
- Serum total bilirubin ≤ 2.5 mg/dL. Note, patients with Gilbert's syndrome may have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their baseline total bilirubin.
- Serum alanine aminotransferase or aspartate aminotransferase < 3 times ULN
- Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography) or MUGA scan
- Patients with second malignancies may be eligible at discretion of PI given acute life threatening nature of untreated AML or higher risk MDS. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible.
Who cannot join
- Patients who have previously undergone allogeneic hematopoietic stem cell transplant will be excluded from this study
- Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368 mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment of solid tumors). See appendix for anthracycline equivalence table.
- Acute promyelocytic leukemia [t(15;17)]
- Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
- Patients who have had conventional intensive cytotoxic induction chemotherapy for treatment of specifically MDS or AML are excluded.
- Patients who have not previously been treated with HMA therapy will be excluded
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- Clinical evidence of active CNS leukemia
- Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)
- Active and uncontrolled infection. Patients with an active infection receiving treatment and hemodynamically stable for 48 hours may be entered into the study
- Known active uncontrolled HIV or hepatitis C infection
- Known hypersensitivity to cytarabine, daunorubicin or liposomal products
- Known history of Wilson's disease or other copper-related disorders
- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation
- Laboratory abnormalities:
- Serum creatinine ≥ 2.0 mg/dL
- Serum total bilirubin > 2.5 mg/dL. Note, patients with Gilbert's syndrome may have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are excluded if their total bilirubin is > 2 times their baseline total bilirubin.
- Serum alanine aminotransferase or aspartate aminotransferase > 3 times ULN
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Stanford, California, 94305
About this study
Official title: A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent
This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Read the detailed description
PRIMARY OBJECTIVES:
Determine efficacy of CPX-351 by measuring the response rate as the sum of complete response (CR) and complete remission with incomplete count recovery (CRi) in older patients (age 60 and older) with: higher risk of myelodysplastic syndrome (MDS) who are refractory/relapsed after prior hypomethylating (HMA) therapy; subjects greater than 75 years old with higher risk MDS who are HMA relapsed/refractory who have progressed to acute myeloid leukemia (AML)); AML with refractory/relapsed disease after prior HMA therapy for AML.
SECONDARY OBJECTIVES:
- Determine the safety of CPX-351, as the frequency of Grade 3 to 5 SAEs
- Determine the duration of remission (DOR) following induction therapy with CPX-351.
- Determine overall survival (OS) at 12 months.
- Determine the early induction mortality (at 30 and 60 days) following CPX-351 following induction therapy.
OUTLINE:
Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5 of each induction cycle.
- 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 proceed to consolidation therapy
- 2nd INDUCTION: Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive the 2nd course of induction therapy. Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) after the 2nd course of induction therapy proceed to consolidation therapy.
- CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.
After completion of study treatment, patients are followed up for up to 1 year.
- Conditions
- Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Being tested
- liposomal cytarabine-daunorubicin CPX-351
- Medical subject headings
- Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
liposomal cytarabine-daunorubicin CPX-351Drug
Also called CPX-351
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Liposomal cytarabine-daunorubicin CPX-351 | Experimental | * 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5.
* 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.
* CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. Receives: Drug: liposomal cytarabine-daunorubicin CPX-351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (RR)
The response rate was determined as the sum of complete response calculated by adding the total complete response (CR) and complete response with incomplete count recovery (CRi). The outcome is reported as the total number without dispersion.
- CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.
- CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.
Measured: Day 42
Secondary outcomes (8)
Complete Response With Incomplete Count Recovery (CRi)
Complete response (CR) with incomplete count recovery (CRi) was determined as the number of participants who achieved CRi after induction therapy. The outcome is reported as the total number or participants without dispersion.
- CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.
- CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.
Measured: Day 42
Complete Response (CR)
Complete response (CR) was determined the number of participants who achieved CR by Day 42 after induction treatment. The outcome is reported as the total number of participants without dispersion.
- CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.
Measured: Day 42
Duration of Remission (DOR) Following Induction With CPX-351
Duration of remission (DOR) was assessed as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until documented lost of response, relapse, or death. The outcome is reported as the median with full range.
- CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.
- CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.
For patients remaining alive, duration of remission (DOR) is reported as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until the most recent assessment.
Measured: Up to 1 year
Overall Survival (OS)
Overall survival (OS) was assessed as the number of participants remaining alive 12 months, starting from date of entry into trial. The outcome is reported as the number of participants (without dispersion).
Measured: At 12 months
Early Induction Mortality (Day 30 After 1st Induction)
Early induction mortality was assessed as the number of participants who died within 30 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion.
Measured: 30 days
Mortality at Day 60 After 1st Induction
Mortality at Day 60 after 1st induction was assessed as the number of participants who died within 60 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion.
Measured: 60 days
Participants Experiencing of Serious Adverse Events
Serious adverse events per participant were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the number of participants that experienced any defined SAE, a number without dispersion.
Measured: Up to 4 weeks after completion of treatment
Serious Adverse Events
Serious adverse events were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the total number of the defined SAEs, a number without dispersion.
Measured: Up to 4 weeks after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study start3 Feb 2014
- Primary completion4 Dec 2017
- Study completion18 Dec 2017
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 Adult Acute Erythroid Leukemia (M6)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rondeep Brar
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Rondeep Brar, Stanford University
- Investigators
- Rondeep Brar, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02019069
- Sponsor's protocol ID
- IRB-28524
- Other IDs
- NCI-2013-01982, HEM0036, P30CA124435
- Status last verified
- Jan 2019
- First submitted
- 25 Nov 2013
- Last updated
- 22 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent
- ClinicalTrials.gov ID
- NCT02019069
- Acronym / sponsor ID
- IRB-28524
- Conditions
- Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Rondeep BrarUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 3 Feb 2014 (actual)
- Primary completion
- 4 Dec 2017 (actual)
- Study completion
- 18 Dec 2017 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Posted 15 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Detailed description
PRIMARY OBJECTIVES:
Determine efficacy of CPX-351 by measuring the response rate as the sum of complete response (CR) and complete remission with incomplete count recovery (CRi) in older patients (age 60 and older) with: higher risk of myelodysplastic syndrome (MDS) who are refractory/relapsed after prior hypomethylating (HMA) therapy; subjects greater than 75 years old with higher risk MDS who are HMA relapsed/refractory who have progressed to acute myeloid leukemia (AML)); AML with refractory/relapsed disease after prior HMA therapy for AML.
SECONDARY OBJECTIVES:
- Determine the safety of CPX-351, as the frequency of Grade 3 to 5 SAEs
- Determine the duration of remission (DOR) following induction therapy with CPX-351.
- Determine overall survival (OS) at 12 months.
- Determine the early induction mortality (at 30 and 60 days) following CPX-351 following induction therapy.
OUTLINE:
Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5 of each induction cycle.
- 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 proceed to consolidation therapy
- 2nd INDUCTION: Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive the 2nd course of induction therapy. Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) after the 2nd course of induction therapy proceed to consolidation therapy.
- CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.
After completion of study treatment, patients are followed up for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liposomal cytarabine-daunorubicin CPX-351 | Experimental | Drug: liposomal cytarabine-daunorubicin CPX-351* 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. * 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. * CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Ability to understand and voluntarily give informed consent
- Age ≥ 60
- Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and high risk MDS by IPSS) along with one of the following:
- Life expectancy > 1 month
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Key exclusion criteria (17 listed)
- Patients who have previously undergone allogeneic hematopoietic stem cell transplant will be excluded from this study
- Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368 mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment of solid tumors). See appendix for anthracycline equivalence table.
- Acute promyelocytic leukemia [t(15;17)]
- Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
- Patients who have had conventional intensive cytotoxic induction chemotherapy for treatment of specifically MDS or AML are excluded.
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 |
|---|---|---|
| liposomal cytarabine-daunorubicin CPX-351Also: CPX-351Given IV | Drug | Liposomal cytarabine-daunorubicin CPX-351 |
Primary outcome
Response Rate (RR)
Time frame: Day 42
The response rate was determined as the sum of complete response calculated by adding the total complete response (CR) and complete response with incomplete count recovery (CRi). The outcome is reported as the total number without dispersion. * CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. * CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.
8 secondary outcomes
Complete Response With Incomplete Count Recovery (CRi)
Time frame: Day 42
Complete Response (CR)
Time frame: Day 42
Duration of Remission (DOR) Following Induction With CPX-351
Time frame: Up to 1 year
Overall Survival (OS)
Time frame: At 12 months
Early Induction Mortality (Day 30 After 1st Induction)
Time frame: 30 days
Mortality at Day 60 After 1st Induction
Time frame: 60 days
Participants Experiencing of Serious Adverse Events
Time frame: Up to 4 weeks after completion of treatment
Serious Adverse Events
Time frame: Up to 4 weeks after completion of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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.
Rondeep Brar, MD principal investigator
Stanford University
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 liposomal cytarabine-daunorubicin CPX-351 in people with Adult Acute Erythroid Leukemia (M6) and Adult Acute Megakaryoblastic Leukemia (M7), run by Rondeep Brar 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 15 inclusion and 17 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 22 Jan 2019. 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?
Yes. Results are posted in the registry (first posted 15 Jan 2019). 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?
Response Rate (RR) (time frame: Day 42). 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 22 Jan 2019.