Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Northwestern University
New York Presbyterian Hospital
University of Southern California
Princess Margaret Hospital, Canada
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01404949
First received: July 27, 2011
Last updated: July 22, 2014
Last verified: July 2014

July 27, 2011
July 22, 2014
July 2011
July 2015   (final data collection date for primary outcome measure)
To determine the rate of molecular remission [ Time Frame: 4 years ] [ Designated as safety issue: No ]
after induction with combined tretinoin and ATO (along with idarubicin in patients with high-risk disease or who develop leukocytosis) in APL.
Same as current
Complete list of historical versions of study NCT01404949 on ClinicalTrials.gov Archive Site
  • To determine the rate of clinical complete remission (CR) and the time to remission [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    after induction with tretinoin and ATO (with idarubicin in patients with high-risk disease or who develop leukocytosis).
  • To determine the proportion of patients in molecular remission [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    after each course of postremission therapy.
  • To determine the disease-free, event-free, and overall survival of patients [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    treated with this program.
  • To determine the toxicity of this treatment program [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    including the early death rate (within 30 days), the incidence of APL differentiation syndrome, the number and length of hospitalizations, the incidence of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), and the effects of treatment on left ventricular ejection fraction (LVEF) Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 will be tabulated.
  • To characterize the differentiation of APL cells during treatment [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    with combined tretinoin and ATO using serial immunophenotyping studies of peripheral blood
  • Explore the in vivo induction of telomerase-dependent cell death [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    by ATRA (Tretinoin) and ATO (Arsenic Trioxide). Bone marrow samples will be analyzed at baseline and at the time of clinical CR for telomerase activity, telomere length and TERT expression
Same as current
Not Provided
Not Provided
 
Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
Phase II Study of Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

The purpose of this study is to find what effects, good and/or bad, treatment with two drugs has on leukemia. The first medicine is tretinoin (also called all-trans retinoic acid, ATRA, or Vesanoid). It is an approved medicine that causes the leukemia cells in APL to mature. It is related to vitamin A. The second is arsenic trioxide (Trisenox). It is an approved medicine for APL that comes back after earlier treatment.

APL is most often treated with tretinoin and standard chemotherapy drugs. These chemotherapy drugs can cause infection and bleeding. They can also damage the heart and normal bone marrow cells. This can lead to a second leukemia years later.

In this study, the investigators are using tretinoin and arsenic trioxide together. Both drugs work to treat APL. They have been used together in only a limited number of people. The investigators want to use these drugs together to reduce the amount of standard chemotherapy and decrease side effects. The patient will receive standard chemotherapy with a drug called idarubicin only if they have a higher chance of the leukemia coming back or a higher risk of side effects.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Promyelocytic Leukemia
Drug: Tretinoin and Arsenic Trioxide
Induction will consist of tretinoin 45 mg/m2 po daily in two divided doses (25 mg/m2 in patients <20 years of age) for 35 days and ATO 0.15 mg/kg IV daily for 35 doses given 5-7 days per week. The drugs will then be discontinued, and the patient will be followed until a clinical complete remission is achieved. Idarubicin 12 mg/m2 IV for 4 doses will be added during induction on day 2 if the presenting WBC is >10,000/μl, or if the WBC increases to 5,000/μl on day 5, 10,000/μl on day 10, or 15,000/μl on day 15, because of the increased risk of the APL differentiation syndrome and relapse in these patients. Dexamethasone 10 mg twice daily with be given on days 1-14 of induction as prophylaxis for the APL differentiation syndrome. All patients will then receive four courses of consolidation with tretinoin 45 mg/m2 po daily (25 mg/m2 in patients <20 years of age) for 15 days and ATO 0.15 mg/kg IV for 25 doses.
Other Names:
  • Patients with high-risk disease will receive intrathecal cytarabine as CNS
  • prophylaxis given by the treating physician during consolidation.
  • These patients will also receive maintenance therapy with additional courses
  • of tretinoin and ATO every 3 months for 2 years. Each maintenance course will
  • consist of tretinoin 45 mg/m2 po daily (25 mg/m2 in patients <20 years of age)
  • for 15 days and ATO 0.15 mg/kg IV for 10 doses.
Experimental: Tretinoin and Arsenic Trioxide
This is a multicenter, phase II trial to study the efficacy of combined tretinoin and ATO in the treatment of newly diagnosed APL in an effort to reduce or eliminate the amount of standard chemotherapy required for long-term remission.
Intervention: Drug: Tretinoin and Arsenic Trioxide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
39
July 2015
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Previously untreated patients with a morphologic diagnosis of APL, confirmed by demonstration of t(15;17) using conventional cytogenetics or florescence in situ hybridization (FISH), or a positive RT-PCR assay for PML-RAR at the subject's local institution.
  • Age ≥18 years. Karnofsky performance status of ≥ 60%.
  • Adequate renal function as demonstrated by a serum creatinine ≤ 2.0 mg/dl or a creatinine clearance of > 60 ml/min.
  • Adequate hepatic function as demonstrated by a bilirubin < 2.0 mg/dl (unless attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 2.5 times the upper limit of normal.
  • Normal cardiac function as demonstrated by a left ventricular ejection fraction ≥ 50% on echocardiogram or MUGA scan.
  • QTc ≤ 500 msec on baseline ECG.
  • Negative serum pregnancy test in women of childbearing potential.
  • Ability to swallow oral medication.
  • Men and women of child-bearing potential must be willing to practice an effective method of birth control during treatment and at least 4 months after treatment is finished.
  • Patients with central nervous system involvement by APL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice.

Exclusion Criteria:

  • Previous treatment for APL, except tretinoin, which may be given for up to 7 days prior to study entry.
  • Active serious infections not controlled by antibiotics.
  • Pregnant women or women who are breast-feeding.
  • Concurrent active malignancy requiring immediate therapy.
  • Clinically significant cardiac disease (NY Heart Association Class III or IV), including chronic arrhythmias, or pulmonary disease.
  • Other serious or life-threatening conditions deemed unacceptable by the principal investigator.
Both
18 Years and older
No
Contact: Jae Park, MD 212-639-4048
Contact: Martin Tallman, MD 212-639-3849
United States,   Canada
 
NCT01404949
11-040
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
  • Northwestern University
  • New York Presbyterian Hospital
  • University of Southern California
  • Princess Margaret Hospital, Canada
  • National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Jae Park, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP