Trial of CPX-351 in Adult Patients With First Relapse Acute Myeloid Leukemia (AML)

This study has been completed.
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Celator Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00822094
First received: January 12, 2009
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

The study investigates if CPX-351 will be a) more effective than the standard intensive salvage AML treatment and b) more tolerable than the standard intensive salvage treatment regimens.

The study compares the investigational product CPX-351 vs the standard intensive salvage treatment for first relapse AML patients.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: CPX-351
Drug: Intensive Salvage Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IIB, Multicenter, Randomized, Open-Label Trial Of CPX-351 (Cytarabine : Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adult Patients ≤ 65 Years Old With AML In First Relapse Following An Initial CR > 1 Month Duration

Resource links provided by NLM:


Further study details as provided by Celator Pharmaceuticals:

Primary Outcome Measures:
  • Percentage Overall Survival at 1 year [ Time Frame: Up to 1 year from randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Remission Rate [ Time Frame: Following 1st induction, following 2nd induction if applicable ] [ Designated as safety issue: No ]
  • Event Free Survival [ Time Frame: Up to 1 year from randomization ] [ Designated as safety issue: No ]
  • Complete Remission Duration [ Time Frame: Following achievement of CR and up to 1 year from randomization ] [ Designated as safety issue: No ]
  • Rate of Aplasia [ Time Frame: Up to 1 year from randomization ] [ Designated as safety issue: No ]
  • Rate of Stem Cell Transplant [ Time Frame: Up to 1 year from randomization ] [ Designated as safety issue: No ]
  • Early induction mortality at day 30 and at day 60 from start of 1st induction [ Time Frame: day 30 and day 60 from 1st induction ] [ Designated as safety issue: Yes ]
  • Late mortality [ Time Frame: following Day 90 from 1st induction ] [ Designated as safety issue: Yes ]
  • Cardiac toxicity by monitoring of left ventricular ejection fraction changes [ Time Frame: Up to 1 year from randomization ] [ Designated as safety issue: Yes ]

Enrollment: 125
Study Start Date: February 2009
Study Completion Date: January 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
CPX-351
Drug: CPX-351
100u/m2 will be administered on study days 1, 3 and 5 as a 90 minute infusion
Active Comparator: B
Investigators choice of an Intensive Salvage Therapy for remission induction (non-palliative) purposes (for example: "HiDAC" (high dose ara-d, anthracycline), "MEC" (mitoxantrone, etoposide, cytarabine), "7 + 3" (cytarabine, daunorubucin))
Drug: Intensive Salvage Therapy
Investigators choice of an Intensive Salvage Therapy as used for remission induction

Detailed Description:

This study is a randomized, open-label, parallel-arm, fixed-dose, standard therapy controlled Phase IIB trial. Study enrollment duration is expected to be approximately 12-18 months. On entry, patients are randomized to receive either CPX-351 or intensive first salvage treatment.

Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR between the two arms.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and voluntarily sign an informed consent form
  • Age ≥18 and ≤65 years at the time of relapse
  • Pathological confirmation of relapsed AML after initial CR of >1 month duration
  • 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 < 2.0 mg/dL
    • Serum alanine aminotransferase or aspartate aminotransferase <3xULN Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss.
  • Cardiac ejection fraction > 50% by echocardiography or MUGA scan
  • All men and women must agree to practice effective contraception during the study period and for 3 months afterward if not otherwise documented to be infertile.

Exclusion Criteria:

  • Patients with active second malignancies are excluded. Patients with second malignancies in remission may be eligible if there is no clinical evidence of active disease, documented by imaging, with tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible. In all cases, the second malignancy and its non-chemotherapy treatment must not interfere with the investigators ability to assess the safety or efficacy of the study treatment
  • Patients with acute promyelocytic leukemia [t(15;17)]
  • Total lifetime anthracycline exposure exceeding the equivalent of 368 mg/m2 of daunorubicin (or equivalent) prior to start of study therapy
  • Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
  • Administration of any antineoplastic therapy within 4 weeks of therapy; intended to treat first relapse. In the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment
  • Clinical evidence of active CNS leukemia
  • Patients with history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in New York Heart Association Class III or IV staging
  • Active and uncontrolled infection. Patients with a bacterial infection receiving treatment with antibiotics may be entered into the study if they are afebrile and hemodynamically stable for >72 hrs.
  • Current evidence of invasive fungal infection (blood or tissue culture); active hepatitis C infection or known HIV infection
  • Hypersensitivity to cytarabine, daunorubicin or liposomal products
  • History of Wilson's disease or other copper-related disorder
  • Patients with a history of severe toxicity related to receiving conventional dose cytarabine in first line treatment (approximately 100mg/m2/d for <7 days) are excluded. Patients who experienced unacceptable toxicities while receiving high dose cytarabine (approximately 3000mg/m2 for 6 doses) will not be treated again with the same regimen, but could be randomized to treatment with conventional dose cytarabine regimens where the risk of major toxicity is less.
  • Woman who are pregnant or breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00822094

  Show 42 Study Locations
Sponsors and Collaborators
Celator Pharmaceuticals
The Leukemia and Lymphoma Society
Investigators
Principal Investigator: Jonathan Kolitz, MD North Shore University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Celator Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00822094     History of Changes
Other Study ID Numbers: CLTR0308-205
Study First Received: January 12, 2009
Last Updated: February 20, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Celator Pharmaceuticals:
Acute
Myeloid
Leukemia
Adult
First
Relapse
AML
Acute Myelogenous leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute myelocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014