Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia (IAPLSG04)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2007 by Christian Medical College, Vellore, India.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Ministry of Science and Technology, India
Information provided by:
Christian Medical College, Vellore, India
ClinicalTrials.gov Identifier:
NCT00517712
First received: August 16, 2007
Last updated: NA
Last verified: August 2007
History: No changes posted
  Purpose

There is very limited data on the use of arsenic trioxide in newly diagnosed patients with acute promyelocytic leukemia. The use of arsenic trioxide was limited to relapsed patients mainly because of the superior efficacy of ATRA as primary therapy for newly diagnosed APML. Though the early study by Niu et al showed 72% remission rates in 11 newly diagnosed patients, the role of arsenic trioxide as primary therapy was limited by the hepatic toxicity seen in this study. Studies from our centre have shown remission rates of 70-75% in newly diagnosed patients with acute promyelocytic leukemia. There was no major toxicity seen related to the administration of arsenic trioxide. Follow up data on these patients continue to show long term remission rates above 70%. These remission rates are similar to the data available in patients with acute promyelocytic leukemia treated with ATRA. Lu et al studied 19 patients treated with oral arsenic (Tetra-arsenic tetra-sulfide) wherein 84% achieved hematological remission with disease free survival of 76% at 3 years. Studies from other groups using arsenic trioxide alone or in combination with ATRA have shown similar remission rates. Arsenic trioxide as primary therapy for patients with newly diagnosed acute promyelocytic leukemia is a very attractive treatment option for developing countries mainly because of the low cost involved along with the favorable toxicity profile. However long term remission data is still not available and the ideal course and duration of treatment still needs to be defined. This multi-center study aims to further clarify the efficacy of this agent in the treatment of newly diagnosed cases of acute promyelocytic leukemia and to study the optimal maintenance regimen.


Condition Intervention Phase
Acute Promyelocytic Leukemia
Drug: Single agent arsenic trioxide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Remission With Arsenic Trioxide in Acute Promyelocytic Leukemia: Indian APL Study Group - IAPLSG

Resource links provided by NLM:


Further study details as provided by Christian Medical College, Vellore, India:

Primary Outcome Measures:
  • Measure complete hematological remission rate [ Time Frame: 60 days ]
  • Measure complete molecular remission rate [ Time Frame: 3 months ]
  • Measure duration of response [ Time Frame: 5 years ]

Secondary Outcome Measures:
  • Document early and late toxicities [ Time Frame: 5 years ]
  • Measure relapse rates [ Time Frame: 5 years ]
  • Measure treatment related mortality [ Time Frame: 60 days ]

Estimated Enrollment: 400
Study Start Date: June 2004
Estimated Study Completion Date: July 2009
Arms Assigned Interventions
Active Comparator: A
Duration of maintenance therapy with single agent ATO of 12 months
Drug: Single agent arsenic trioxide
duration of maintenance therapy, 6 months versus 12 months
Active Comparator: B
Duration of maintenance therapy with single agent ATO for 6 months
Drug: Single agent arsenic trioxide
duration of maintenance therapy, 6 months versus 12 months

  Hide Detailed Description

Detailed Description:

This multicenter trial will study the clinical and molecular response among patients with newly diagnosed acute promyelocytic leukemia (APL) who fulfill the inclusion and exclusion criteria.

Patients included in this trial should have been diagnosed to have Acute Promyelocytic Leukemia morphologically on FAB criteria. This is sufficient to initiate therapy with arsenic trioxide (ATO) but this diagnosis has to be confirmed using either Fluorescent in situ hybridization (FISH) for t(15;17) or reverse transcriptase polymerase chain reaction assay (RT-PCR) for PML-RARalpha transcripts within 7 days of inclusion into the study.

All these patients would have in the absence of this study received only palliative therapy due to the lack of resources to support standard chemotherapy.

Women who are pregnant will not be considered for this study.

Treatment Protocol: All patients who are included in this study will be initiated on treatment with ATO. Arsenic tri-oxide (10 mg/10ml) will be diluted in 500 ml of Dextrose Saline (only glass bottles to be used) and infused intravenously over 3 - 4 hours once a day.

No premedication is required prior to administration of the drug. The dosage schedule for administration will be as follows:

Adults: 10 mg once a day Children or adults <45kg: 0.15 mg/kg/day (maximum dose = 10mg) once a day

The total courses of therapy will be as follows:

Induction therapy: Induction therapy will be continued till ANC> 1.5 x 10e9/L and Platelet count > 100 x 10e9/L along with the absence of abnormal promyelocytes in peripheral smear on 2 consecutive occasions. Once this is achieved, bone marrow studies will be done to assess remission. If the bone marrow shows < 5% of myeloblasts and promyelocytes along with a normocellular to mildly hypocellular marrow, arsenic can be stopped. If not in CR, arsenic is continued for an additional 2 weeks and a repeat bone marrow is done to confirm CR. Arsenic tri-oxide will be given for a maximum of 60 days following which the patient would be considered a non-responder/partial responder and excluded from further treatment. If bone marrow shows <5% blasts and promyelocytes at 60 days but peripheral blood count criteria for CR are not fulfilled, patient can be still be continued on the study regimen.

Consolidation therapy: All patients who achieve CR will receive consolidation therapy for a period of 28 days after an interval of 4 weeks from achieving hematological CR. The dosage and mode of administration will be similar to the schedule followed in induction.

Maintenance therapy: All patients who are in molecular CR at the end of consolidation therapy will be randomized into 2 groups:

Group A: This group will receive 12 months of maintenance therapy. ATO will be administered for 10 days every month for a period of 12 months.

Group B: This group will receive 6 months of maintenance therapy. ATO will be administered for 10 days every month for a period of 6 months.

All patients who continue to be RT-PCR positive at the end of consolidation will not be randomized and will continue to receive all the courses of maintenance treatment. Subsequent therapy will be individualized based on the molecular monitoring results.

A total of 400 patients will be recruited at the time of initiation into this study. We expect a loss to follow up/treatment failure/death of approximately 10% of the study population and hence 360 patients will be randomized into the final 2 arms of the study ie maintenance therapy for 12 months versus 6 months after completing the consolidation therapy.

Patients with CNS disease will be treated with therapeutic Radiotherapy and intrathecal chemotherapy using Cytosine, Hydrocortisone and Methotrexate.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients included in this trial should have been diagnosed to have Acute Promyelocytic Leukemia morphologically on FAB criteria. This is sufficient to initiate therapy with arsenic tri-oxide but this diagnosis has to be confirmed using either Fluorescent in situ hybridization (FISH) for t(15;17) or reverse transcriptase polymerase chain reaction assay (RT-PCR) for PML-RARalpha transcripts within 7 days of inclusion into the study.
  • All these patients would have in the absence of this study received only palliative therapy due to the lack of resources to support standard chemotherapy.

Exclusion Criteria:

  • Women who are pregnant
  • Patients with acute promyelocytic leukemia who are found on standard karyotyping/ FISH/RTPCR to have t(11;17) or t(5;17).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517712

Contacts
Contact: Vikram Mathews, MD 91-416-2282891 vikram@cmcvellore.ac.in
Contact: Mammen Chandy, MD 91-416-2282169 mammen@cmcvellore.ac.in

Locations
India
St. Johns Hospital Recruiting
Bangalore, Karnataka, India, 560034
Contact: Cecil Ross, MD    91-80-22065000    ross@satyam.net.in   
Principal Investigator: Cecil Ross, MD         
Kidwai Memorial Institute of Oncology Not yet recruiting
Bangalore, Karnataka, India, 560029
Principal Investigator: P P Bapsy, MD         
Regional Cancer Center Recruiting
Trivandrum, Kerala, India, 695011
Contact: Geetha Narayanan, MD    91-471-2442541    geenarayanan@yahoo.com   
Principal Investigator: Krishnan Nair, MD         
KEM Hospital Recruiting
Mumbai, Maharastra, India, 400012
Contact: Farah Jijina, MD    91-22-22872904    f_jijina@hotmail.com   
Principal Investigator: Farrah Jijina, MD         
Tata Memorial Hospital Recruiting
Mumbai, Maharastra, India, 400012
Contact: Reena Nair, MD    91-22-4146750    reenanair@email.com   
Principal Investigator: Purvish Parikh, MD         
Prince Aly Khan Hospital Not yet recruiting
Mumbai, Maharastra, India, 400010
Contact: Tapan Saikia, MD    91-22-23777800    tsaikias@yahoo.co.in   
Principal Investigator: Tapan Saikia, MD         
Sahyadri Speciality Hospital Recruiting
Pune, Maharastra, India
Contact: Shashi Apte, MD    91-20-25403040    sashi@pn3.vsnl.net.in   
Principal Investigator: Shashi Apte, MD         
Netaji Subhash Chandra Bose Cancer Research Institute Recruiting
Kolkata, West Bengal, India, 700016
Contact: Ashis Mukherjee, MD    91-33-22291049    hmcwt@dataone.in   
Principal Investigator: Ashish Mukherjee, MD         
Institute Rotary Cancer Hospital Recruiting
New Delhi, India, 110029
Contact: Atul Sharma, MD    91-11-26589490    atul1@hotmail.com   
Principal Investigator: Vinod Kochupillai, MD         
Sponsors and Collaborators
Christian Medical College, Vellore, India
Ministry of Science and Technology, India
Investigators
Principal Investigator: Mammen Chandy, MD Christian Medical College, Vellore, India
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00517712     History of Changes
Other Study ID Numbers: IAPLSG2004, BT/PR4460/Med/14/531/2003
Study First Received: August 16, 2007
Last Updated: August 16, 2007
Health Authority: India: Institutional Review Board

Keywords provided by Christian Medical College, Vellore, India:
Acute promyelocytic leukemia
Arsenic trioxide
Molecular remission
Toxicity profile
Maintenance therapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014