All-trans Retinoic Acid, and Arsenic +/- Gemtuzumab - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00413166

Purpose

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.

Condition	Intervention	Phase
Acute Promyelocytic Leukemia	Drug: All-Trans Retinoic Acid (ATRA) Drug: Arsenic Trioxide (ATO) Drug: Idarubicin	Phase II

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:	Treatment of Acute Promyelocytic Leukemia (APL) With All-Trans Retinoic Acid, and Arsenic +/- Gemtuzumab

Resource links provided by NLM:

Genetics Home Reference related topics: acute promyelocytic leukemia

MedlinePlus related topics: Arsenic Cancer Leukemia

Drug Information available for: Idarubicin hydrochloride Idarubicin Gemtuzumab ozogamicin Tretinoin Arsenic trioxide

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Complete Response (CR) Rate [ Time Frame: Daily during 7 days of induction, then 2 times weekly ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	September 2006
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Induction 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) Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1 Drug: Arsenic Trioxide (ATO) Induction: 0.15 mg/kg daily IV beginning day 1 Drug: Idarubicin 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) 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.
Experimental: Maintenance 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: Idarubicin 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) 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.

Arms

Assigned Interventions

Experimental: Induction

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)

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

Drug: Arsenic Trioxide (ATO)

Induction: 0.15 mg/kg daily IV beginning day 1

Drug: Idarubicin

12 mg/m2 one dose only (may be given on day 1 to 5 of induction)
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.

Experimental: Maintenance

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: Idarubicin

12 mg/m2 one dose only (may be given on day 1 to 5 of induction)
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.

Detailed Description:

All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells).

If you are found to be eligible to take part in this study, you will begin induction. During induction, you will receive ATRA, by mouth starting on Day 1. You will also receive ATO through a needle in your vein over 2 hours starting on Day 1. You will continue receiving the drugs every day until your bone marrow no longer shows APL cells.

If you had a high white blood cell count at screening, you will receive idarubicin through a needle in your vein over about 30 minutes one dose only on any day of Day 1 through 5.

During induction, blood (about 1-3 tablespoons) will be drawn every day during Week 1, and then 2 times a week after that. This blood will be drawn for routine tests.

During induction (about 21-28 days after beginning treatment), you will have a bone marrow aspirate to check the status of the disease. This may be performed more often if the doctor thinks it is needed.

If you achieve a complete remission during the induction phase, you will continue to the maintenance phase. During the maintenance phase, you will receive ATO by vein over 2 hours Monday-Friday for 4 weeks. After the 4 weeks of receiving the study drug, you will have a 4-week period "off" (when no study drug is given). ATRA is given by mouth every day for 2 weeks. This 2 weeks is followed by 2 additional weeks when no study drug will be given. You will continue to take ATRA until treatment with ATO is complete.

During maintenance, blood (about 1-3 tablespoons) will be drawn before every 4-week cycle of ATO, and then every week for routine tests. You will also have an ECG before every 4 week cycle when you take ATO.

If you do not achieve a complete remission during induction you will be taken off study.

If at any point during the study your white blood cell count rises above 10,000, you will receive idarubicin by vein over 30 minutes.

You will remain in the hospital for about the first 7 days of induction. After that, you must remain in Houston for the next 3-4 weeks. Once in the maintenance phase, you may be treated at home, but must return to M. D. Anderson for study visits.

After maintenance is complete, you will have follow-up visits for an additional 2 years. If at any time during the active study or follow-up the disease gets worse or intolerable side effects occur, you will be taken off the study.

If you had a low or high white blood cell count when you joined the study, you will have follow-up visits every 3 months for 2 years. At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.

This is an investigational study. Idarubicin, ATRA and ATO are FDA approved and commercially available. However, their use in this study and in this combination is considered investigational. Its use in APL patients is investigational. Up to 80 patients will take part in the study. All will be enrolled at M. D. Anderson.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413166

Contacts

Contact: Farhad Ravandi-Kashani, MD

713-792-7305

fravandi@mdanderson.org

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Farhad Ravandi-Kashani, MD 713-792-7305 fravandi@mdanderson.org

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Farhad Ravandi-Kashani, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

MD Anderson's website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00413166 History of Changes
Other Study ID Numbers:	2006-0706
Study First Received:	December 15, 2006
Last Updated:	September 2, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Acute Promyelocytic Leukemia
APL
ATRA
All-Trans Retinoic Acid

Arsenic Trioxide
Theophylline
Gemtuzumab

Additional relevant MeSH terms:

Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Idarubicin
Arsenic trioxide

Gemtuzumab
Tretinoin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on February 09, 2012