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

NCT ID: NCT01404949

Last Updated: 2021-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2021-02-01

Brief Summary

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.

Detailed Description

Induction will consist of tretinoin 45 mg/m2 po daily (rounded up to the nearest 10mg) 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 (rounded up to the nearest 10mg) (25 mg/m2 in patients <20 years of age) for 15 days and ATO 0.15 mg/kg IV for 25 doses.

Patients with high-risk disease or who received Idarubicin during Induction may receive intrathecal cytarabine as CNS prophylaxis given by the treating physician during consolidation, at the discretion of the site PI. High-risk 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. Disease status will be monitored with serial analyses of peripheral blood samples using RT-PCR for PML-RARα mRNA. Patients will be followed until relapse, death, loss to follow-up, or removal from study.

Induction therapy can be given as an inpatient or outpatient. Consolidation and maintenance treatments will be given as an outpatient. Consolidation may also be given at the patient's local institution. Intrathecal cytarabine treatments will be administered as an outpatient.

Conditions

Acute Promyelocytic Leukemia

Keywords

Tretinoin; all-trans retinoic acid; ATRA; Vesanoid; Arsenic Trioxide; ATO; Trisenox; 11-040

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tretinoin and Arsenic Trioxide

Intervention Type: DRUG

See Detailed Description

Interventions

Tretinoin and Arsenic Trioxide

See Detailed Description

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: collaborator

New York Presbyterian Hospital

OTHER

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: collaborator

Princess Margaret Hospital, Canada

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jae Park, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

University of Southern California

Los Angeles, California, United States

Northwestern University

Evanston, Illinois, United States

National Heart, Lung, and Blood Institute (NIH)

Bethesda, Maryland, United States

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, United States

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

New York Presbyterian Hospital-Weill Medical College of Cornell University

New York, New York, United States

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Princess Margaret Hospital/Ontario Cancer Institute

Toronto, Ontario, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

11-040

Identifier Type: -

Identifier Source: org_study_id