A Novel Sequential Treatment of Salvage and Reduced Intensity Conditioning (RIC) Chemotherapy for Allogeneic Stem-Cell Transplantation (SCT) for Primary Refractory and Relapsed Acute Myelogenous Leukemia (AML)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Weill Medical College of Cornell University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Celator Pharmaceuticals
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00875693
First received: April 2, 2009
Last updated: January 3, 2011
Last verified: January 2011
  Purpose

This open-label Phase I study is designed to determine the maximum tolerated dose (MTD) for CPX-351 followed by a reduced intensity conditioning regimen and incorporates a dose-escalation schedule that sequentially enrolls 6 dosing cohorts. After the determination of the MTD, the investigator reserves the option to enroll up to 10 additional subjects in an expanded safety cohort(s) at the MTD.

Refractory and relapsed AML patients who meet standard institutional criteria to undergo sequential induction/reduced intensity conditioning allogeneic transplants will be offered a transplant from a related or unrelated donor (full match or 1 antigen mismatch). Cord blood transplants will not be used in this study.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Drug: CPX-351
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Novel Sequential Treatment of Salvage and Reduced Intensity Conditioning RIC) Chemotherapy for Allogeneic Stem-Cell Transplantation (SCT)for Primary Refractory and Relapsed Acute Myelogenous Leukemia

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • To determine the toxicity and safety of the regimen [ Time Frame: cohort dependent ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: June 2009
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose level 1
60 units/m2 days -28, -26 and -24
Drug: CPX-351
CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio.
Experimental: Dose Level 2
80 units/m2 days -28, -26 and -24
Drug: CPX-351
CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio.
Experimental: Dose level 3
100 units/m2 days -28, -26 and -24
Drug: CPX-351
CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio.
Experimental: Dose Level 4
120 units/m2 days -28, -26 and -24
Drug: CPX-351
CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio.
Experimental: Dose Level 5
140 units/m2 days -28, -26 and -24
Drug: CPX-351
CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio.
Experimental: Dose Level 6
160 units/m2 days -28, -26 and -24
Drug: CPX-351
CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients are included, if they fulfill at least one of the following criteria defining refractory or relapsed AML according to previously established criteria 1-3: (1) Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy. (2) First relapse. (3) Relapse refractory to salvage chemotherapy (4) Second or subsequent relapse.
  2. Patients with MDS, either RAEB I or RAEB II
  3. Age between 18 and 70 years old.
  4. Patients must have a Karnofsky Performance Status > 70.
  5. Each patient must be willing to participate as a research subject and must sign an informed consent form.
  6. If the patient has a history of a prior malignancy, they must be without any evidence of disease of that prior malignancy for at least 2 years before being eligible for transplant on this protocol. This excludes skin cancers that may have been excised within that 2 year period.
  7. Patients must have adequate physical function measured by:

    1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.
    2. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless liver is involved with the disease or there is congenital benign hyperbilirubinemia.
    3. Renal: serum creatinine within normal range for age or if serum creatinine is outside the normal range, then CrCl > 60-ml/min.
    4. Pulmonary: asymptomatic or if symptomatic, DLCO > 45% of predicted (corrected for hemoglobin)

Exclusion Criteria:

  1. Impaired renal function with a measured or calculated creatinine clearance of less than 60 ml/min.
  2. Impaired hepatic function defined as a bilirubin greater than 1.5 x upper limit of normal or ALT or AST greater than 3 x normal.
  3. Serious active or uncontrolled infection (Infections are controlled when patients are afebrile and hemodynamically stable for 72 hours) or medical condition.
  4. Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test.
  5. Impaired pulmonary function with a DLCO less than 45% predicted.
  6. Impaired cardiac function with an ejection fraction less than 50% of predicted by echocardiogram or MUGA.
  7. Prior daunorubicin therapy with a cumulative dose of more than 368 mg/m2 or equivalent. The anthracycline agents commonly used in treating myeloid malignancies are doxorubicin, idarubicin and mitoxantron.

    For example, a patient who receives 7 + 3 (daunorubicin 180 mg/m2) for induction and MEC (mitoxantrone 48 mg/m2) for salvage. The cumulative daunorubicin equivalent is 180 + (48x2) = 278 mg/m2.

  8. Other systemic anticancer therapy or ongoing toxicities from such therapy.
  9. Patients with a history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, congestive heart failure), resulting in heart failure by New York Heart Association Class III or IV staging.
  10. Patients with Wilson disease or other Cu-related disorders.
  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: NCT00875693

Contacts
Contact: Usama Gergis, MD usg2001@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Usama Gergis, MD       usg2001@med.cornell.edu   
Principal Investigator: Usama Gergis, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Celator Pharmaceuticals
Investigators
Principal Investigator: Usama Gergis, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Usama Gergis, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT00875693     History of Changes
Other Study ID Numbers: 0812010140
Study First Received: April 2, 2009
Last Updated: January 3, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
AML
leukemia
MDS

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on July 31, 2014