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Acute Promyelocytic LeukemiaPhase 2/3IAPLSG04NCT00517712

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

A Phase 2/3 study testing Single agent arsenic trioxide in people with Acute Promyelocytic Leukemia, run by Christian Medical College, Vellore, India at 9 sites in India.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Any age
Conditions the study is for
Acute Promyelocytic Leukemia
What is being tested?
Single agent arsenic trioxide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
400 participants
Where
9 sitesIndia
Study dates
Jun 2004to Jul 2009
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).

Trial locations and contacts

9 sites in 1 country.

Vikram Mathews, MD contact

91-416-2282891

vikram@cmcvellore.ac.in

Mammen Chandy, MD contact

91-416-2282169

mammen@cmcvellore.ac.in

9 sites in 1 country

India9 sites, 9 recruiting
  • Kidwai Memorial Institute of Oncology

    Bangalore, Karnataka, 560029

    P P Bapsy, MD

    Not yet recruiting
  • St. Johns Hospital

    Bangalore, Karnataka, 560034

    Cecil Ross, MD, 91-80-22065000, ross@satyam.net.in

    Cecil Ross, MD

    Recruiting
  • Netaji Subhash Chandra Bose Cancer Research Institute

    Kolkata, West Bengal, 700016

    Ashis Mukherjee, MD, 91-33-22291049, hmcwt@dataone.in

    Ashish Mukherjee, MD

    Recruiting
  • Prince Aly Khan Hospital

    Mumbai, Maharashtra, 400010

    Tapan Saikia, MD, 91-22-23777800, tsaikias@yahoo.co.in

    Tapan Saikia, MD

    Not yet recruiting
  • KEM Hospital

    Mumbai, Maharashtra, 400012

    Farah Jijina, MD, 91-22-22872904, f_jijina@hotmail.com

    Farrah Jijina, MD

    Recruiting
  • Tata Memorial Hospital

    Mumbai, Maharashtra, 400012

    Reena Nair, MD, 91-22-4146750, reenanair@email.com

    Purvish Parikh, MD

    Recruiting
  • Institute Rotary Cancer Hospital

    New Delhi, New Delhi, 110029

    Atul Sharma, MD, 91-11-26589490, atul1@hotmail.com

    Vinod Kochupillai, MD

    Recruiting
  • Sahyadri Speciality Hospital

    Pune, Maharashtra

    Shashi Apte, MD, 91-20-25403040, sashi@pn3.vsnl.net.in

    Shashi Apte, MD

    Recruiting
  • Regional Cancer Center

    Trivandrum, Kerala, 695011

    Geetha Narayanan, MD, 91-471-2442541, geenarayanan@yahoo.com

    Krishnan Nair, MD

    Recruiting

Other trials in India

About this study

Official title: Molecular Remission With Arsenic Trioxide in Acute Promyelocytic Leukemia: Indian APL Study Group - IAPLSG

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.

Read the 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.

Being tested
Single agent arsenic trioxide
Keywords
Acute promyelocytic leukemia, Arsenic trioxide, Molecular remission, Toxicity profile, Maintenance therapy
Medical subject headings
Leukemia, Promyelocytic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Single agent arsenic trioxideDrug

    duration of maintenance therapy, 6 months versus 12 months

Study groups in NCT00517712
Study groupRoleWhat they receive
AActive comparatorDuration of maintenance therapy with single agent ATO of 12 months
Receives: Drug: Single agent arsenic trioxide
BActive comparatorDuration of maintenance therapy with single agent ATO for 6 months
Receives: Drug: Single agent arsenic trioxide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Measure complete hematological remission rate

    Measured: 60 days

  2. Measure complete molecular remission rate

    Measured: 3 months

  3. Measure duration of response

    Measured: 5 years

Secondary outcomes (3)
  1. Document early and late toxicities

    Measured: 5 years

  2. Measure relapse rates

    Measured: 5 years

  3. Measure treatment related mortality

    Measured: 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2007 (estimated)
  2. Study startJun 2004
  3. Study completionJul 2009 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00517712
Sponsor's protocol ID
IAPLSG2004
Other IDs
BT/PR4460/Med/14/531/2003
Acronym
IAPLSG04
Status last verified
Aug 2007
First submitted
16 Aug 2007
Last updated
17 Aug 2007
Results posted
No
Data monitoring committee
No

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.

    PubMed 16352810
  • 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.

    PubMed 15356649
  • 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.

    PubMed 12210810
  • 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.

    PubMed 11547528
  • 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.

    PubMed 15477216
  • 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.

    PubMed 16525498
  • 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.

    PubMed 17606455

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Single agent arsenic trioxide in people with Acute Promyelocytic Leukemia, run by Christian Medical College, Vellore, India at 9 sites in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Vikram Mathews, MD (91-416-2282891, vikram@cmcvellore.ac.in), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measure complete hematological remission rate (time frame: 60 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00517712, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2007.

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