Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00528450
• Collaborator: National Cancer Institute (NCI) (NIH), Cephalon (Industry)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Tretinoin may help cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as arsenic trioxide and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tretinoin together with arsenic trioxide with or without idarubicin may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving tretinoin together with arsenic trioxide with or without idarubicin works in treating patients with acute promyelocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: arsenic trioxide; Drug: idarubicin; Drug: tretinoin	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the rate of molecular remission after induction therapy comprising tretinoin (ATRA) and arsenic trioxide (ATO) (along with idarubicin in patients with leukocytosis) in patients with acute promyelocytic leukemia (APL).

Secondary

• To determine the rate of clinical complete remission and the time to remission after induction therapy.

• To determine the proportion of patients in molecular remission after each course of postremission therapy and to use these findings to direct the number of consolidation courses with ATRA and idarubicin that are administered.

• To determine the disease-free survival and overall survival of patients treated with this regimen.

• To determine the toxicity of this treatment regimen, including the number and length of hospitalizations, the incidence of secondary myelodysplastic syndromes or acute myeloid leukemia, and the effects of treatment on LVEF.

• To characterize the differentiation of APL cells during treatment with combined ATRA and ATO using serial immunophenotyping studies of peripheral blood and bone marrow.

• To compare the results of quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays performed on bone marrow and peripheral blood.

OUTLINE:

• Induction therapy: Patients receive tretinoin orally twice daily and arsenic trioxide IV over 1-4 hours once daily until a marrow remission is documented or for 60 days, whichever comes first. Patients with leukocytosis (WBC > 10,000/μL) also receive idarubicin IV over 10-15 minutes beginning on day 2 and continuing every other day for 4 doses. Patients who achieve a clinical complete remission (CR) proceed to consolidation therapy. If a marrow remission is not achieved after 60 days, the patient is removed from the study.

• Consolidation therapy:

• Consolidation courses 1, 2, and 3: Beginning 3-6 weeks after documentation of clinical CR, patients receive consolidation therapy comprising tretinoin orally twice daily for 15 days and arsenic trioxide IV over 1-4 hours once daily 5 days a week for 5 weeks. Consolidation therapy repeats every 3-6 weeks for 3 courses.

Patients who have a negative PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay after consolidation course 2 proceed to maintenance therapy after receiving consolidation course 3. Patients who have a negative PML-RARα transcript by RT-PCR assay after consolidation course 3, proceed to consolidation course 4 followed by maintenance therapy. Patients who have a positive PML-RARα transcript by RT-PCR assay after consolidation courses 2 and 3 proceed to consolidation courses 4 and 5.

• Consolidation course 4: Beginning 3-6 weeks after completion of consolidation course 3, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 4 days.

• Consolidation course 5: Beginning 3-6 weeks after completion of consolidation course 4, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 3 days.

Patients who remain positive for the PML-RARα transcript after 5 courses of consolidation therapy are removed from the study. Patients who have a negative PML-RARα transcript after 5 courses of consolidation therapy proceed to maintenance therapy.

• Maintenance therapy: Beginning approximately 3 months after completion of the final consolidation course, patients receive tretinoin orally twice daily for 15 days. Treatment repeats every 3 months for up to 2 years.

Disease status will be monitored with serial analyses of bone marrow and 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tretinoin and Arsenic Trioxide With or Without Idarubicin See Outline for details	Drug: arsenic trioxide; Drug: idarubicin; Drug: tretinoin

Outcome Measures

Primary Outcome Measures

1. Molecular Remission Rate [2 years]

   # of patients with Complete Remission

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Morphologic diagnosis of acute promyelocytic leukemia (APL), confirmed by one of the following:

• Demonstration of t(15;17) using conventional cytogenetics or fluorescence in situ hybridization (FISH)

• Positive PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay

• Patients with CNS involvement by APL are eligible

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Creatinine ≤ 2.0 mg/dL or creatinine clearance > 60 mL/min

• Bilirubin < 2.0 mg/dL (unless attributed to Gilbert disease)

• Alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)

• AST and ALT ≤ 2.5 ULN

• LVEF ≥ 50% on echocardiogram or MUGA scan

• QTc ≤ 500 msec on baseline ECG

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 4 months after the completion of study treatment

• No active serious infections not controlled by antibiotics

• No other concurrent active malignancy requiring immediate therapy

• No clinically significant cardiac disease (New York Heart Association class III or IV heart disease), including chronic arrhythmias

• No pulmonary disease

• No other serious or life-threatening condition deemed unacceptable by the principal investigator

PRIOR CONCURRENT THERAPY:

• No prior treatment for APL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)
• Cephalon

Investigators

• Principal Investigator: Joseph G. Jurcic, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Peter Maslak, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00528450
• Other Study ID Numbers: 07-108; P30CA008748; MSKCC-07108; CEPHALONO-MSKCC-07108
• First Posted: Sep 12, 2007
• Last Update Posted: Jan 29, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: adult acute promyelocytic leukemia (M3); adult acute myeloid leukemia with t(15;17)(q22;q12); untreated adult acute myeloid leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute; Idarubicin; Arsenic Trioxide; Tretinoin

Study Results

Participant Flow

Arm/Group Title	All Patients
Arm/Group Description	Tretinoin and Arsenic Trioxide With or Without Idarubicin
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	Tretinoin and Arsenic Trioxide With or Without Idarubicin
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Molecular Remission Rate
Description	# of patients with Complete Remission
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Tretinoin and Arsenic Trioxide With or Without Idarubicin
Measure Participants	1
Number [participants]	1 100%

Adverse Events

Arm/Group Title	All Patients
Arm/Group Description	Tretinoin and Arsenic Trioxide With or Without Idarubicin
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
ALT, SGPT	1/1 (100%)	1
AST, SGOT	1/1 (100%)	1
Hemoglobin	1/1 (100%)	1
Leukocytes (total WBC)	1/1 (100%)	1
Lymphopenia	1/1 (100%)	1
Neutrophils/granulocytes (ANC/AGC)	1/1 (100%)	1
Platelets	1/1 (100%)	1
Gastrointestinal disorders
Vomiting	1/1 (100%)	1
General disorders
Pain - Head/headache	1/1 (100%)	1
Pain - Pain NOS	1/1 (100%)	1
Infections and infestations
Infection, other	1/1 (100%)	1
Metabolism and nutrition disorders
Alkaline phosphatase	1/1 (100%)	1
Bilirubin (hyperbilirubinemia)	1/1 (100%)	1
Glucose, high (hyperglycemia)	1/1 (100%)	1
Phosphate, low (hypophosphatemia)	1/1 (100%)	1
Potassium, high (hyperkalemia)	1/1 (100%)	1
Nervous system disorders
Dizziness	1/1 (100%)	1
Psychiatric disorders
Mood alteration - Anxiety	1/1 (100%)	1
Skin and subcutaneous tissue disorders
Pruritus/itching	1/1 (100%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.