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NCT02019069

CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Completed Phase 2 Results posted Last updated 22 January 2019
What this trial tests

Phase 2 trial testing liposomal cytarabine-daunorubicin CPX-351 in Adult Acute Erythroid Leukemia (M6) in 11 participants. Completed in 18 December 2017.

Timeline
3 February 2014
Primary endpoint
4 December 2017
18 December 2017

Quick facts

Lead sponsorRondeep Brar
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment11
Start date3 February 2014
Primary completion4 December 2017
Estimated completion18 December 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Rondeep Brar — full company profile →

Who can join

60 and older, any sex, with Adult Acute Erythroid Leukemia (M6) or Adult Acute Megakaryoblastic Leukemia (M7). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Response Rate (RR) Primary · 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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3513
Complete Response With Incomplete Count Recovery (CRi) Secondary · Day 42

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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3511
Complete Response (CR) Secondary · Day 42

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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3512
Duration of Remission (DOR) Following Induction With CPX-351 Secondary · Up to 1 year

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

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-35118525 – 329
Overall Survival (OS) Secondary · At 12 months

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).

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3511
Early Induction Mortality (Day 30 After 1st Induction) Secondary · 30 days

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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3512
Mortality at Day 60 After 1st Induction Secondary · 60 days

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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3513
Participants Experiencing of Serious Adverse Events Secondary · Up to 4 weeks after completion of treatment

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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3515
Serious Adverse Events Secondary · Up to 4 weeks after completion of treatment

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.

GroupValue95% CI
Liposomal Cytarabine-daunorubicin CPX-3518

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 4 weeks after completion of treatment]. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Liposomal Cytarabine-daunorubicin CPX-351
Serious: 5/11 (45%)
Deaths: 10/11

Serious adverse events (8 terms)

ReactionSystemLiposomal Cytarabine-dauno…
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaRespiratory, thoracic and mediastinal disorders
Adult repiratory distress syndrome (ARDS)Respiratory, thoracic and mediastinal disorders
Cardio-pulmonary arrestCardiac disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
ChillsGeneral disorders
AnemiaBlood and lymphatic system disorders
Neoplasms - Other, Acute myelogenous leukemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (43 terms — click to expand)

ReactionSystemLiposomal Cytarabine-dauno…
Febrile neutropeniaBlood and lymphatic system disorders
DiarrheaGastrointestinal disorders
Mucositis oralGastrointestinal disorders
ConstipationGastrointestinal disorders
FeverGeneral disorders
HallucinationsPsychiatric disorders
Abdominal painGastrointestinal disorders
ColitisGastrointestinal disorders
HematuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Thrombotic thrombocytopenic purpuraBlood and lymphatic system disorders
Lung infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
DizzinessNervous system disorders
Blood and lymphatic system disorders, other - clot in cheekBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Cardiac disorders, other - tachycardiaCardiac disorders
Sinus tachycardiaCardiac disorders
Eye disorders, other - eye itchingEye disorders
PapilledemaEye disorders
NauseaGastrointestinal disorders
Rectal hemorrhageGastrointestinal disorders
Pain, hipGeneral disorders
Pain, legGeneral disorders
FatigueGeneral disorders
Investigations, other - fluid overloadInvestigations
Hepatobiliary disorders, other - hyperbilirubinemiaMetabolism and nutrition disorders
Anorexia (decreased food consumption)Metabolism and nutrition disorders
HypertriglyceridemiaMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder, other - broken legMusculoskeletal and connective tissue disorders
Brachial plexopathyNervous system disorders
HeadacheNervous system disorders
Peripheral motor neuropathyNervous system disorders
Renal and urinary disorders, other - urinary discomfortRenal and urinary disorders
AspirationRespiratory, thoracic and mediastinal disorders
Epistaxis (nose bleed)Respiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders, other - chest tightnessRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Febrile neutropenia, Pneumonia, Adult repiratory distress syndrome (ARDS), Cardio-pulmonary arrest, Respiratory failure, Chills, Anemia, Neoplasms - Other, Acute myelogenous leukemia.

Data from ClinicalTrials.gov NCT02019069 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Nanoparticles in the clinic: An update.
    Anselmo AC, Mitragotri S. · · 2019 · cited 976× · PMID 31572799 · DOI 10.1002/btm2.10143
  2. Nanoparticles in the clinic.
    Anselmo AC, Mitragotri S. · · 2016 · cited 773× · PMID 29313004 · DOI 10.1002/btm2.10003
  3. Clinical Translation of Nanomedicine.
    Min Y, Caster JM, Eblan MJ, Wang AZ. · · 2015 · cited 495× · PMID 26088284 · DOI 10.1021/acs.chemrev.5b00116
  4. Current challenges and unmet medical needs in myelodysplastic syndromes.
    Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. · · 2021 · cited 67× · PMID 34045662 · DOI 10.1038/s41375-021-01265-7
  5. Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML.
    Chen EC, Fathi AT, Brunner AM. · · 2018 · cited 35× · PMID 29928134 · DOI 10.2147/ott.s141212

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