All-trans Retinoic Acid, and Arsenic +/- Idarubicin

NCT00413166 | Completed Phase 2 Results

• 2 other identifiers: 2006-0706NCI-2012-01395
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of arsenic trioxide (ATO) with ATRA and possibly idarubicin is effective in treating patients with newly-diagnosed APL.

Conditions

Acute Promyelocytic Leukemia

Keywords

Acute Promyelocytic Leukemia; APL; ATRA; All-Trans Retinoic Acid; Arsenic Trioxide; Theophylline; Gemtuzumab

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate

  Response defined as CR (marrow with \<5% blasts and no abnormal promyelocytes together with neutrophil count \>1000 and platelet count \>100,000) and toxicity as Acute promyelocytic leukemia (APL) differentiation syndrome, arrhythmia, peripheral neuropathy. Bone marrow aspirate performed to check the status of the disease.

  1 month, up to day 85 of treatment

Study Arms (3)

Induction ATRA + ATO + Idarubicin

EXPERIMENTAL

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATRA 45 mg/m2 daily by mouth beginning day 1; ATO 0.15 mg/kg by vein daily beginning on day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days starting on day 1.

Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin

Maintenance

EXPERIMENTAL

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATO 0.15 mg/kg by vein over 2 hours Monday-Friday for 4 weeks, then a 4-week break. ATRA 45 mg/m2 by mouth every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin

Induction ATRA + ATO + GO

EXPERIMENTAL

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) + Gemtuzumab Ozogamicin (GO) ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1; ATO 0.15 mg/kg IV daily beginning on day 1; GO 9 mg/m2 on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1. Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed.

Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin; Drug: Gemtuzumab Ozogamicin

Interventions

All-Trans Retinoic Acid (ATRA) DRUG

Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1

Induction ATRA + ATO + GO; Induction ATRA + ATO + Idarubicin; Maintenance

Arsenic Trioxide (ATO) DRUG

Induction: 0.15 mg/kg daily IV beginning day 1

Induction ATRA + ATO + GO; Induction ATRA + ATO + Idarubicin; Maintenance

Idarubicin DRUG

1. 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) 2. If either ATRA or ATO are discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses will be administered once every 4 to 5 weeks (depending on the recovery of counts) until 28 weeks has elapsed from the Complete Recovery date.

Also known as: Idamycin

Induction ATRA + ATO + GO; Induction ATRA + ATO + Idarubicin; Maintenance

Gemtuzumab Ozogamicin DRUG

Induction: 9 mg/m2 on day 1 of induction

Induction ATRA + ATO + GO

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of APL based on the presence of the PML-RAR alpha fusion gene by cytogenetics, PCR, or POD test.
• Provision of written informed consent.
• Patients in whom therapy for APL was initiated on an emergent basis are eligible

You may not qualify if:

• First trimester of pregnancy (ATRA is teratogenic)
• Corrected QT (QTC) interval must not be greater than 480 milliseconds.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Tretinoin; Arsenic Trioxide; Idarubicin; Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Farhad Ravandi-Kashani, Professor, Leukemia
• Organization: The University of Texas (UT) MD Anderson Cancer Center

fravandi@mdanderson.org

7137927734

Study Officials

• Farhad Ravandi-Kashani, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2006
• First Posted: December 19, 2006
• Study Start: December 1, 2006
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: May 7, 2019
• Results First Posted: April 18, 2019

Record last verified: 2019-04

Locations

US (1)