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
  Purpose

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.


Condition Intervention Phase
Acute Promyelocytic Leukemia
Drug: Tretinoin and Arsenic Trioxide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 39
Study Start Date: July 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01404949

Contacts
Contact: Jae Park, MD 212-639-4048
Contact: Martin Tallman, MD 212-639-3849

Locations
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Vinod Pullarkat, MD         
Principal Investigator: Vinod Pullarkat, MD         
United States, Illinois
Northwestern University Recruiting
Evanston, Illinois, United States, 60208
Contact: Jessica Altman, MD         
Principal Investigator: Jessica Altman, MD         
United States, Maryland
National Heart, Lung, and Blood Institute (NIH) Not yet recruiting
Bethesda, Maryland, United States, 20824
Contact: Neal Young, MD         
Principal Investigator: Neal Young, MD         
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Jae Park, MD    212-639-4048      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Jae Park, MD    212-639-4048      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Jae Park, MD    212-639-4048      
Contact: Martin Tallman, MD    212-639-3849      
Principal Investigator: Jae Park, MD         
New York Presbyterian Hospital-Weill Medical College of Cornell University Recruiting
New York, New York, United States, 10065
Contact: Gail Roboz, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Jae Park, MD    212-639-4048      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Jae Park, MD    212-639-4048      
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Matt Kalaycio, MD         
Principal Investigator: Matt Kalaycio, MD         
Canada, Ontario
Princess Margaret Hospital/Ontario Cancer Institute Not yet recruiting
Toronto, Ontario, Canada
Contact: Andre Schuh, MD         
Principal Investigator: Andre Schuh, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Northwestern University
New York Presbyterian Hospital
University of Southern California
Princess Margaret Hospital, Canada
Investigators
Principal Investigator: Jae Park, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01404949     History of Changes
Other Study ID Numbers: 11-040
Study First Received: July 27, 2011
Last Updated: July 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Tretinoin
all-trans retinoic acid
ATRA
Vesanoid
Arsenic Trioxide
ATO
Trisenox
11-040

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Arsenic trioxide
Tretinoin
Antineoplastic Agents
Dermatologic Agents
Keratolytic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014