- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00517712
Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia (IAPLSG04)
Molecular Remission With Arsenic Trioxide in Acute Promyelocytic Leukemia: Indian APL Study Group - IAPLSG
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Vikram Mathews, MD
- Phone Number: 91-416-2282891
- Email: vikram@cmcvellore.ac.in
Study Contact Backup
- Name: Mammen Chandy, MD
- Phone Number: 91-416-2282169
- Email: mammen@cmcvellore.ac.in
Study Locations
-
-
-
New Delhi, India, 110029
- Recruiting
- Institute Rotary Cancer Hospital
-
Contact:
- Atul Sharma, MD
- Phone Number: 91-11-26589490
- Email: atul1@hotmail.com
-
Principal Investigator:
- Vinod Kochupillai, MD
-
-
Karnataka
-
Bangalore, Karnataka, India, 560029
- Not yet recruiting
- Kidwai Memorial Institute of Oncology
-
Principal Investigator:
- P P Bapsy, MD
-
Bangalore, Karnataka, India, 560034
- Recruiting
- St. Johns Hospital
-
Contact:
- Cecil Ross, MD
- Phone Number: 91-80-22065000
- Email: ross@satyam.net.in
-
-
Kerala
-
Trivandrum, Kerala, India, 695011
- Recruiting
- Regional Cancer Center
-
Contact:
- Geetha Narayanan, MD
- Phone Number: 91-471-2442541
- Email: geenarayanan@yahoo.com
-
Principal Investigator:
- Krishnan Nair, MD
-
-
Maharastra
-
Mumbai, Maharastra, India, 400010
- Not yet recruiting
- Prince Aly Khan Hospital
-
Contact:
- Tapan Saikia, MD
- Phone Number: 91-22-23777800
- Email: tsaikias@yahoo.co.in
-
Principal Investigator:
- Tapan Saikia, MD
-
Mumbai, Maharastra, India, 400012
- Recruiting
- KEM hospital
-
Contact:
- Farah Jijina, MD
- Phone Number: 91-22-22872904
- Email: f_jijina@hotmail.com
-
Principal Investigator:
- Farrah Jijina, MD
-
Mumbai, Maharastra, India, 400012
- Recruiting
- Tata Memorial Hospital
-
Contact:
- Reena Nair, MD
- Phone Number: 91-22-4146750
- Email: reenanair@email.com
-
Principal Investigator:
- Purvish Parikh, MD
-
Pune, Maharastra, India
- Recruiting
- Sahyadri Speciality Hospital
-
Contact:
- Shashi Apte, MD
- Phone Number: 91-20-25403040
- Email: sashi@pn3.vsnl.net.in
-
Principal Investigator:
- Shashi Apte, MD
-
-
West Bengal
-
Kolkata, West Bengal, India, 700016
- Recruiting
- Netaji Subhash Chandra Bose Cancer Research Institute
-
Contact:
- Ashis Mukherjee, MD
- Phone Number: 91-33-22291049
- Email: hmcwt@dataone.in
-
Principal Investigator:
- Ashish Mukherjee, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: A
Duration of maintenance therapy with single agent ATO of 12 months
|
duration of maintenance therapy, 6 months versus 12 months
|
Active Comparator: B
Duration of maintenance therapy with single agent ATO for 6 months
|
duration of maintenance therapy, 6 months versus 12 months
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measure complete hematological remission rate
Time Frame: 60 days
|
60 days
|
Measure complete molecular remission rate
Time Frame: 3 months
|
3 months
|
Measure duration of response
Time Frame: 5 years
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Document early and late toxicities
Time Frame: 5 years
|
5 years
|
Measure relapse rates
Time Frame: 5 years
|
5 years
|
Measure treatment related mortality
Time Frame: 60 days
|
60 days
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Mammen Chandy, MD, Christian Medical College, Vellore, India
Publications and helpful links
General Publications
- Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. doi: 10.1182/blood-2005-08-3532. Epub 2005 Dec 13.
- George B, Mathews V, Poonkuzhali B, Shaji RV, Srivastava A, Chandy M. Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience. Leukemia. 2004 Oct;18(10):1587-90. doi: 10.1038/sj.leu.2403480.
- Mathews V, Balasubramanian P, Shaji RV, George B, Chandy M, Srivastava A. Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: a single center experience. Am J Hematol. 2002 Aug;70(4):292-9. doi: 10.1002/ajh.10138.
- Mathews V, Chandy M, Srivastava A. Arsenic trioxide in the management of acute promyelocytic leukaemia. Natl Med J India. 2001 Jul-Aug;14(4):215-22.
- George B, Mathews L, Balasubramanian P, Shaji RV, Srivastava A, Chandy M. Molecular remission with arsenic trioxide in patients with newly diagnosed acute promyelocytic leukemia. Haematologica. 2004 Oct;89(10):1266-7.
- Mathews V, Desire S, George B, Lakshmi KM, Rao JG, Viswabandya A, Bajel A, Srivastava VM, Srivastava A, Chandy M. Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity. Leukemia. 2006 May;20(5):881-3. doi: 10.1038/sj.leu.2404165. No abstract available.
- Mathews V, Thomas M, Srivastava VM, George B, Srivastava A, Chandy M. Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen. Haematologica. 2007 Jul;92(7):994-5. doi: 10.3324/haematol.10802.
Study record dates
Study Major Dates
Study Start
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IAPLSG2004
- BT/PR4460/Med/14/531/2003
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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