Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Promyelocytic, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Acute Graft Versus Host Disease

Acute Promyelocytic Leukemia

Anti-Inflammatory Agents

Antineoplastic Agents

All Drugs and Chemicals

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Dermatologic Agents

Vasodilator Agents

Respiratory System Agents

Anti-Infective Agents

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Tretinoin

Idarubicin

Theophylline

Arsenic Trioxide

Gemtuzumab

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Keratolytic Agents

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

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.

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.

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.

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

All-Trans Retinoic Acid (ATRA)

Induction: 0.15 mg/kg daily IV beginning day 1

Arsenic Trioxide (ATO)

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.

Gemtuzumab Ozogamicin

Farhad Ravandi-Kashani, MD

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.

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 this multicenter study. All will be enrolled at M. D. Anderson.

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

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

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.

M.D. Anderson Cancer Center

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC\>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

Post CR

1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a "2-weeks on -2-weeks off" basis until therapy with ATO completed.

ATRA + ATO: Low Risk (WBC<10,000)

Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days.

ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1.

Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date.

ATRA+ATO+IDA: High Risk (WBC >10,000)

Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction 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.

Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

ATO+ATRA+GO

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Farhad Ravandi-Kashani, Professor, Leukemia

Of the 57 participants treated on the ATRA + ATO: Low Risk treatment arm, 56 participants were evaluable for response.

Complete Response (CR) Rate

ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction 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.

Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete.

Overall Study

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Micronutrients

Vitamins

Ascorbic Acid

Trace Elements

Antioxidants

Protective Agents

Vitamin C

Arsenic Trioxide (ATO) given at 0.25 mg/kg/day intravenously for 25 days over a 35-day period.

Ascorbic Acid given at 1000 mg/day intravenously every other day that ATO is given

Ascorbic Acid 1000 mg every other day for 25 days

Dan Douer, MD

This clinical research study is for patients with acute myelogenous leukemia (in short AML) that did not respond to previous treatment or unable to receive chemotherapy.

Arsenic has been used as a drug for many centuries. While arsenic containing drugs were used in the past for cancer treatments, the major use of arsenic in western countries has been for the treatment of uncommon tropical illnesses, such as sleeping sickness. Recently, some new information suggests that arsenic in a form called arsenic trioxide may also be useful to treat some cancers of the blood, such as leukemia, lymphoma and myeloma. Studies from China and the USA showed that patients with a type of blood cancer called acute promyelocytic leukemia, whose disease failed to respond to other treatments, responded very well to arsenic trioxide. Studies done in laboratories in the United States have shown that arsenic can kill AML cells growing in culture dishes.

Ascorbic acid (vitamin C), a natural supplement in our diet, has long been involved with cancer prevention. Laboratory tests have shown that although arsenic trioxide by itself can kill AML cells in the test tube, when vitamin C is added to arsenic trioxide in a test tube, the death of the leukemia cells increases significantly.

The purpose of this study is to find out if the combination of arsenic trioxide (Trisenox) and ascorbic acid is effective in the treatment of patients who have AML. The second purpose is to study how the two drugs affect cells in the laboratory. Samples from the blood and bone marrow (the part of the body that makes blood cells) will be collected, at specific times during treatment, in order to study them in the laboratory. By studying blood and marrow cells, researchers hope to learn the mechanisms by which the drugs work.

Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia

Phase II Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-APL Acute Myelogenous Leukemia

Complete Remission (CR): ANC \>=1000/mcl, Platelet count \>=100,000/mcl, Bone marrow \<5% blasts. Complete Remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \<1,000/mcl and/or platelet count \<100,000/mcl. Patients who failed to achieve CR or CRi after two cycles were considered treatment failures. Patients who did not complete at least two cycles were not evaluated for response.

Patients who received any amount of ATO plus Ascorbic Acid are included in the safety analyses.

University of Southern California

All subjects received ATO 0.25 mg/kg/day intravenously for 25 days over a 35-day period and Ascorbic Acid 1000 mg/day intravenously every other day that ATO is given

Arsenic Trioxide (ATO) Plus Ascorbic Acid

All participants were included in the analysis.

Victoria Soto, Project Specialist, Clinical Investigations Support Office

Treatment Failure

Not Evaluable

All subjects who received at least 2 cycles of treatment as part of this study are included in the analysis of response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
All-trans Retinoic Acid, and Arsenic +/- Idarubicin	NCT00413166	Acute Promyeloc...	All-Trans Retin... Arsenic Trioxid... Idarubicin Gemtuzumab Ozog...	-	M.D. Anderson Cancer Center
Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia	NCT00184054	Acute Myelogeno...	Arsenic Trioxid... Ascorbic Acid	18 Years -	University of Southern California

Spots Global Cancer Trial Database for arsenic trioxide (ato)