Relapsed Acute Promyelocytic LeukemiaPhase 2PIAPLNCT01950611
Proteasome Inhibition in Acute Promyelocytic Leukemia
A Phase 2 study testing Bortezomib in people with Relapsed Acute Promyelocytic Leukemia, run by Christian Medical College, Vellore, India at 1 site in India.
Trial summary
The clinical outcome of relapsed acute promyelocytic leukemia (APL) is poor with current standard of care approaches. Additionally, standard of care warrants an autologous stem cell transplant to be done once molecular remission is achieved. Unfortunately, the majority of our patients cannot afford this procedure. Read more about this study
- Who is it for?
- Ages 1 year to 75 years
- Conditions the study is for
- Relapsed Acute Promyelocytic Leukemia
- What is being tested?
- Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteIndia
- Study dates
- May 2013to May 2018
- Phase
- Phase 2
- 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 1 year to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of relapsed t(15;17)(PML-RARα) positive APL confirmed by reverse transcriptase polymerase chain reaction (RT-PCR).
- Normal cardiac function with normal electrocardiogram (QTc less than 500 msec) within 48 hours of study entry.
- Patient or guardian willing to give informed consent / assent. Must not have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.
- Patients may have received hydroxyurea, 48 hours or less of all trans retnoic acid (ATRA), and 1 dose of an anthracycline and still be eligible for participation in this study.
- Life expectancy of at least 2 weeks after entry on study. vi. No age limit for entry into study. vii. ECOG performance score 0, 1, or 2. viii. Fertile patients must agree to use an effective barrier method of contraception (e.g., latex condom, diaphragm, or cervical cap) to avoid pregnancy while on therapy and for 3 years following the discontinuation of therapy.
- Have a negative serum or urine pregnancy test prior to the first dose of therapeutic drugs (if patient is a female of childbearing potential). If breast feeding they should be willing to stop breast feeding.
Who cannot join
- Intracranial bleed at diagnosis. ii. ECOG performance score 3 and above. iii. Severe uncontrolled infection, fulminant sepsis at diagnosis or documented pneumonia.
- History of cardiac arrhythmia; symptomatic coronary heart disease; uncontrollable arterial hypertension (diastolic blood pressure > 115 mm Hg); severe psychiatric disease or other concomitant diseases which do not comply with the criteria for the participation in the study.
- Acute hepatitis (Bilirubin ≥ 5mg% or liver enzymes ≥ 4 times above laboratory normal value) vi. Acute renal failure or serum creatinine ≥ 2 mg% not reversed by hydration. vii. Patients suffering from an additional malignant tumor. No past history of receiving therapy for another malignancy, apart from squamous cell carcinoma or basal cell carcinoma of the skin.
- Pregnancy or lactation. ix. Patients with proven intolerance to the study drugs x. Inability, missing willingness or anticipated lack of compliance by the PI to participate in the study. Must not have any other severe concurrent disease and/or uncontrolled medical conditions, which, in the judgment of the investigator, could predispose patients to unacceptable safety risks or compromise compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Department of Haematology, Christian Medical College
Vellore, Tamil Nadu, 632004
Vikram Mathews, 914162282891, vikram@cmcvellore.ac.in
Biju George, MD. DM
About this study
Official title: Phase II Study to Evaluate the Role of Bortezomib in the Management of Relapsed Acute Promyelocytic Leukemia
The clinical outcome of relapsed acute promyelocytic leukemia (APL) is poor with current standard of care approaches. Additionally, standard of care warrants an autologous stem cell transplant to be done once molecular remission is achieved. Unfortunately, the majority of our patients cannot afford this procedure. We have previously reported the clinical outcome of relapsed patients who were managed without a stem cell transplants and showed that the event free survival at 5 years is less than 35%. Pre-clinical data reported from our laboratory demonstrates that there is significant synergy between arsenic trioxide (ATO; which is the accepted standard of care agent for relapsed APL) and Bortezomib (a proteasome inhibitor). We have evaluated this combination extensively in-vitro and this data was accepted as an oral presentation at the American Society of Hematology (ASH) meeting in 2011. More recently we have also reported the potential mechanism for this synergy (Poster at ASH 2012). We also have mouse model data which supports these findings. We plan to move this combination of ATO based therapy combined with Bortezomib to a Phase II clinical trial to validate these observations. The anticipated potential is that we will have a combination therapy that is less expensive, cost effective and safe with comparable clinical outcomes to those treated with the more expensive standard of care which includes an autologous stem cell transplant and which the majority of our patients cannot afford.
- Conditions
- Relapsed Acute Promyelocytic Leukemia
- Being tested
- Bortezomib
- Keywords
- acute promyelocytic leukemia, arsenic trioxide, proteasome inhibition, bortezomib
- 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.
BortezomibDrug
Combination of arsenic trioxide with bortezomib in the treatment of relapsed acute promyelocytic leukemia
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib in treatment | Experimental | Not described Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Non hematological toxicity to be monitored
Measured: 5 years
Secondary outcomes (1)
Efficacy
- Proportion of patients that achieve molecular remission at the end of induction
- Relapse free, event free and overall survival on long term follow up with this protocol.
- Long term toxicity profile of this combination therapy
- Duration of cytopenia with this combination in induction
- Documentation of support care required and total cost of administering this regimen.
- Performance status prior to consolidation therapy, each maintenance course and at the end of the regimen.
- Molecular remission status on follow up for 5 years
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2013 (estimated)
- Study startMay 2013
- Primary completionMay 2018 (estimated)
- Study completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed Acute Promyelocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christian Medical College, Vellore, India
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vikram Mathews, Christian Medical College, Vellore, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01950611
- Sponsor's protocol ID
- IRB 8225 27/02/13
- Acronym
- PIAPL
- Status last verified
- Sep 2013
- First submitted
- 22 Sep 2013
- Last updated
- 25 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kulkarni U, Ganesan S, Alex AA, Palani H, David S, Balasundaram N, Venkatraman A, Thenmozhi M, Jeyaseelan L, Korula A, Devasia A, Abraham A, Janet NB, Balasubramanian P, George B, Mathews V. A phase II study evaluating the role of bortezomib in the management of relapsed acute promyelocytic leukemia treated upfront with arsenic trioxide. Cancer Med. 2020 Apr;9(8):2603-2610. doi: 10.1002/cam4.2883. Epub 2020 Feb 14.
PubMed 32059085
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Evaluate the Role of Bortezomib in the Management of Relapsed Acute Promyelocytic Leukemia
- ClinicalTrials.gov ID
- NCT01950611
- Acronym / sponsor ID
- PIAPL / IRB 8225 27/02/13
- Conditions
- Relapsed Acute Promyelocytic Leukemia
- Keywords
- acute promyelocytic leukemia, arsenic trioxide, proteasome inhibition, bortezomib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Christian Medical College, Vellore, IndiaUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- May 2018 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 25 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The clinical outcome of relapsed acute promyelocytic leukemia (APL) is poor with current standard of care approaches. Additionally, standard of care warrants an autologous stem cell transplant to be done once molecular remission is achieved. Unfortunately, the majority of our patients cannot afford this procedure. We have previously reported the clinical outcome of relapsed patients who were managed without a stem cell transplants and showed that the event free survival at 5 years is less than 35%. Pre-clinical data reported from our laboratory demonstrates that there is significant synergy between arsenic trioxide (ATO; which is the accepted standard of care agent for relapsed APL) and Bortezomib (a proteasome inhibitor). We have evaluated this combination extensively in-vitro and this data was accepted as an oral presentation at the American Society of Hematology (ASH) meeting in 2011. More recently we have also reported the potential mechanism for this synergy (Poster at ASH 2012). We also have mouse model data which supports these findings. We plan to move this combination of ATO based therapy combined with Bortezomib to a Phase II clinical trial to validate these observations. The anticipated potential is that we will have a combination therapy that is less expensive, cost effective and safe with comparable clinical outcomes to those treated with the more expensive standard of care which includes an autologous stem cell transplant and which the majority of our patients cannot afford.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib in treatment | Experimental | Drug: Bortezomib |
Who may qualify
- Ages
- 1 year to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of relapsed t(15;17)(PML-RARα) positive APL confirmed by reverse transcriptase polymerase chain reaction (RT-PCR).
- Normal cardiac function with normal electrocardiogram (QTc less than 500 msec) within 48 hours of study entry.
- Patient or guardian willing to give informed consent / assent. Must not have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.
- Patients may have received hydroxyurea, 48 hours or less of all trans retnoic acid (ATRA), and 1 dose of an anthracycline and still be eligible for participation in this study.
- Life expectancy of at least 2 weeks after entry on study. vi. No age limit for entry into study. vii. ECOG performance score 0, 1, or 2. viii. Fertile patients must agree to use an effective barrier method of contraception (e.g., latex condom, diaphragm, or cervical cap) to avoid pregnancy while on therapy and for 3 years following the discontinuation of therapy.
Key exclusion criteria (4 listed)
- Intracranial bleed at diagnosis. ii. ECOG performance score 3 and above. iii. Severe uncontrolled infection, fulminant sepsis at diagnosis or documented pneumonia.
- History of cardiac arrhythmia; symptomatic coronary heart disease; uncontrollable arterial hypertension (diastolic blood pressure > 115 mm Hg); severe psychiatric disease or other concomitant diseases which do not comply with the criteria for the participation in the study.
- Acute hepatitis (Bilirubin ≥ 5mg% or liver enzymes ≥ 4 times above laboratory normal value) vi. Acute renal failure or serum creatinine ≥ 2 mg% not reversed by hydration. vii. Patients suffering from an additional malignant tumor. No past history of receiving therapy for another malignancy, apart from squamous cell carcinoma or basal cell carcinoma of the skin.
- Pregnancy or lactation. ix. Patients with proven intolerance to the study drugs x. Inability, missing willingness or anticipated lack of compliance by the PI to participate in the study. Must not have any other severe concurrent disease and/or uncontrolled medical conditions, which, in the judgment of the investigator, could predispose patients to unacceptable safety risks or compromise compliance with the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibCombination of arsenic trioxide with bortezomib in the treatment of relapsed acute promyelocytic leukemia | Drug | Bortezomib in treatment |
Primary outcome
Safety
Time frame: 5 years
Non hematological toxicity to be monitored
1 secondary outcome
Efficacy
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2013.
- Derived from this study: PubMed 32059085Kulkarni U, Ganesan S, Alex AA, Palani H, David S, Balasundaram N, Venkatraman A, Thenmozhi M, Jeyaseelan L, Korula A, Devasia A, Abraham A, Janet NB, Balasubramanian P, George B, Mathews V. A phase II study evaluating the role of bortezomib in the management of relapsed acute promyelocytic leukemia treated upfront with arsenic trioxide. Cancer Med. 2020 Apr;9(8):2603-2610. doi: 10.1002/cam4.2883. Epub 2020 Feb 14.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Relapsed Acute Promyelocytic Leukemia, run by Christian Medical College, Vellore, India at 1 site 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 6 inclusion and 4 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 25 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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. DM (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?
Safety (time frame: 5 years). 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 NCT01950611, which also lists 1 linked publication.
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 25 Sep 2013.