Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT00517712
Other study ID # IAPLSG2004
Secondary ID BT/PR4460/Med/14
Status Recruiting
Phase Phase 2/Phase 3
First received August 16, 2007
Last updated August 16, 2007
Start date June 2004
Est. completion date July 2009

Study information

Verified date August 2007
Source Christian Medical College, Vellore, India
Contact Vikram Mathews, MD
Phone 91-416-2282891
Email vikram@cmcvellore.ac.in
Is FDA regulated No
Health authority India: Institutional Review Board
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 400
Est. completion date July 2009
Est. primary completion date
Accepts healthy volunteers No
Gender Both
Age group N/A and older
Eligibility 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
Single agent arsenic trioxide
duration of maintenance therapy, 6 months versus 12 months

Locations

Country Name City State
India Kidwai Memorial Institute of Oncology Bangalore Karnataka
India St. Johns Hospital Bangalore Karnataka
India Netaji Subhash Chandra Bose Cancer Research Institute Kolkata West Bengal
India KEM Hospital Mumbai Maharastra
India Prince Aly Khan Hospital Mumbai Maharastra
India Tata Memorial Hospital Mumbai Maharastra
India Institute Rotary Cancer Hospital New Delhi
India Sahyadri Speciality Hospital Pune Maharastra
India Regional Cancer Center Trivandrum Kerala

Sponsors (2)

Lead Sponsor Collaborator
Christian Medical College, Vellore, India Ministry of Science and Technology, India

Country where clinical trial is conducted

India, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2005 Dec 13. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Measure complete hematological remission rate 60 days
Primary Measure complete molecular remission rate 3 months
Primary Measure duration of response 5 years
Secondary Document early and late toxicities 5 years
Secondary Measure relapse rates 5 years
Secondary Measure treatment related mortality 60 days
See also
  Status Clinical Trial Phase
Completed NCT00520208 - Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL Phase 2
Suspended NCT04996030 - A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia Phase 1
Recruiting NCT02899169 - Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF) Phase 3
Terminated NCT00852709 - Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias Phase 1
Recruiting NCT04793919 - Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia Phase 2
Recruiting NCT02938858 - French Registry of First-line Treatment of Acute Promyelocytic Leukemia N/A
Recruiting NCT02991066 - Role of Microparticles in the Coagulopathy of Acute Promyelocytic Leukemia
Terminated NCT00985530 - Tamibarotene and Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia Phase 1
Withdrawn NCT00670150 - New Retinoid Agent Combined With Arsenic Trioxide for Untreated Acute Promyelocytic Leukemia Phase 2
Recruiting NCT01064570 - AIDA 2000 Guidelines Phase 2
Completed NCT01472107 - Study on Number and Outcome of Pregnancy in Acute Promielocitic Leukaemia (APL) Patients Treated With Chemotherapy
Active, not recruiting NCT03096496 - Long-term QoL in Acute Promyelocytic Leukemia Treated With ATO or Standard Chemotherapy
Completed NCT00465933 - Treatment of Acute Promyelocytic Leukemia With All-Trans Retinoic Acid (ATRA) and Idarubicin (AIDA) Phase 4
Active, not recruiting NCT02688140 - Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia Phase 3
Active, not recruiting NCT01987297 - Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL Phase 4
Terminated NCT00907582 - ASCT for Relapsed APL After Molecular Remission Phase 2
Completed NCT01902329 - A Safety Study of SGN-CD33A in AML Patients Phase 1
Completed NCT01404949 - Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy Phase 2
Completed NCT00504764 - Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO) Phase 4
Completed NCT00408278 - Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005) Phase 4