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

Condition(s) targeted: Acute Promyelocytic Leukemia

Intervention: Tretinoin and Arsenic Trioxide (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Memorial Sloan-Kettering Cancer Center

Official(s) and/or principal investigator(s):
Jae Park, MD, Principal Investigator, Affiliation: Memorial Sloan-Kettering Cancer Center

Overall contact:
Jae Park, MD, Phone: 212-639-4048

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.

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To determine the rate of molecular remission

Secondary outcome:

To determine the rate of clinical complete remission (CR) and the time to remission

To determine the proportion of patients in molecular remission

To determine the disease-free, event-free, and overall survival of patients

To determine the toxicity of this treatment program

To characterize the differentiation of APL cells during treatment

Explore the in vivo induction of telomerase-dependent cell death

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Jae Park, MD, Phone: 212-639-4048

University of Southern California, Los Angeles, California 90033, United States; Not yet recruiting
Vinod Pullarkat, MD
Vinod Pullarkat, MD, Principal Investigator

Northwestern University, Evanston, Illinois 60208, United States; Recruiting
Jessica Altman, MD
Jessica Altman, MD, Principal Investigator

National Heart, Lung, and Blood Institute (NIH), Bethesda, Maryland 20824, United States; Not yet recruiting
Neal Young, MD
Neal Young, MD, Principal Investigator

Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States; Recruiting
Jae Park, MD, Phone: 212-639-4048
Martin Tallman, MD, Phone: 212-639-3849
Jae Park, MD, Principal Investigator

New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, New York 10065, United States; Recruiting
Gail Roboz, MD

Cleveland Clinic, Cleveland, Ohio 44195, United States; Not yet recruiting
Matt Kalaycio, MD
Matt Kalaycio, MD, Principal Investigator

Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Ontario, Canada; Not yet recruiting
Andre Schuh, MD
Andre Schuh, MD, Principal Investigator

Memorial Sloan-Kettering Cancer Center

Starting date: July 2011
Last updated: January 14, 2013