Acute Lymphoblastic LeukemiaNCT01540812
Treatment of Acute Lymphoblastic Leukemia HIGH RISK BCR / ABL NEGATIVE IN ADULTS
An observational study of Acute Lymphoblastic Leukemia, run by PETHEMA Foundation at 1 site in Spain.
Trial summary
Trial protocol intended the optimization of induction treatment with: 1. Inclusion of PEG-ASP in induction and in the three blocks of consolidation. 2. Reduction of the dose of daunorubicin, and recent studies have shown that the use of high doses of anthracyclines has not brought higher response rates or longer… Read more about this study
- Who is it for?
- Ages 15 to 60 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Vincristine in induction, Daunorubicin in induction and Prednisone in induction
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 418 participants
- Where
- 1 siteSpain
- Study dates
- Feb 2012to 1 Dec 2019
- Phase
- Observational
- 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 15 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: ALL patients
Who may be able to join
- ALL de novo high-risk criteria
- Age 15-55 years (55-60 years patients will be included at the discretion of the medical team that will attend)
- No prior treatment, except Emergency leukapheresis Emergency treatment of hyperleukocytosis with hydroxyurea Urgent cranial irradiation (one dose) for CNS leukostasis Mediastinal irradiation for urgent superior vena cava syndrome
- General condition suitable scale (ECOG 0-2), or> 2 if due to ALL
- Negative pregnancy test for women of childbearing age
- Written informed consent because, although the protocol does not include the use of investigational drugs, biological samples sent there for them
Who cannot join
- L3 type ALL or mature phenotype B (sIg +) or cytogenetic abnormalities characteristic of mature B-ALL (t (8; 14), t (2, 8), t (8; 22)). For these patients is available BURKIMAB protocol.
- LAL Ph (BCR-ABL) positive. For these patients have the protocol ALL-Ph-08 (if under 55) or LALOPh (if over 55).
- Lymphoid blast crisis of chronic myeloid leukemia
- Biphenotypic acute leukemia or bilinear according to the criteria of EGIL group
- Undifferentiated acute leukemias
- Patients with a history of coronary artery disease, valvular or hypertensive heart disease, contraindicating the use of anthracyclines
Show all 14Show fewer
- Patients with chronic phase of activity
- Patients with severe chronic respiratory failure
- Kidney failure due to ALL
- Serious neurological disorder not due to the LAL
- History of pancreatitis
- Pregnancy or breastfeeding
- Mental or psychiatric illness preventing informed consent is given for sending samples or properly follow the study
- General condition affected, not attributable to the ALL
Trial locations and contacts
1 site in 1 country.
About this study
Trial protocol intended the optimization of induction treatment with:
- Inclusion of PEG-ASP in induction and in the three blocks of consolidation.
- Reduction of the dose of daunorubicin, and recent studies have shown that the use of high doses of anthracyclines has not brought higher response rates or longer duration
- Replacing the poor cytological response at day 14 by the level of ER at the end of induction as a criterion to decide the further treatment (consolidation or second induction), so as to have only one criterion (the ER) throughout the study to decision making.
Read more
For another hand, reducing non-essential drugs consolidation blocks to try to reduce toxicity during it, and replace the ASP E. coli in induction and consolidation of PEG-ASP to ensure a more sustained asparagine depletion. Also, increasing the dose of methotrexate (3 to 5 g/m2) in patients with ALL-T, since there is recent evidence of a higher response rate with this strategy.
Performing an allo-HSCT early (after one cycle of consolidation) for patients with inadequate level of ER after two cycles of induction or in those patients who required two courses of induction and have obtained proper ER after the second.
Conducting studies of RD centrally by cytofluorometry following Euroflow consensus standards, to avoid bias in making treatment decisions
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Vincristine in induction, Daunorubicin in induction, Prednisone in induction, Metotrexato in induction, Cytarabine in induction
- Keywords
- Acute Lymphoblastic Leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vincristine in inductionDrug
Daunorubicin in inductionDrug
Prednisone in inductionDrug
Metotrexato in inductionDrug
Cytarabine in inductionDrug
Hydrocortisone in inductionDrug
Idarubicin in induction-2Drug
Fludarabine in induction-2Drug
Ara-C in induction-2Drug
G-CSF in induction-2Drug
Dexamethasone in consolidation-1Drug
Vincristrine in consolidation-1Drug
Metotrexato in consolidation-1Drug
PEG-ASP in consolidation-1Drug
Dexamethasone in consolidation-2Drug
ARA-C in consolidation-2Drug
PEG-ASP in consolidation-2Drug
Dexamethasone in consolidation-3Drug
Vincristine in consolidation-3Drug
Metotrexato in consolidation-3Drug
PEG-ASP in consolidation-3Drug
allogeneic HSCTProcedure or surgery
Allo HSCT with reduced-intensity conditioningProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud | Vincristine in induction:5 mg/m2 i.v. days 1, 8, 15 and 22 in induction phase Daunorubicin in induction 45 mg/m2 i.v. days 1, 8, 15 and 22 Prednisone in induction: 60 mg/m2/ day, i.v. o p.o., days 1 to 14; 30 mg/m2/day, i.v. o p.o., days 15 to 21; 15 mg/m2/day i.v. o p.o., days 21 to 28 Metotrexato 12 mg days 1 and 22 (intrathecal) Cytarabine (ARA-C): 30 mg days 1 and 22 (intrathecal) Hydrocortisone: 20 mg days 1 and 22 (intrathecal) Idarubicin-induction 2 12 mg/m2, i.v., days 1, 3 and 5 Fludarabine in induction-2: Fludarabine 30 mg/m2, i.v., days, 1 to 5 Receives: Drug: Vincristine in induction; Drug: Daunorubicin in induction; Drug: Prednisone in induction; Drug: Metotrexato in induction; Drug: Cytarabine in induction; Drug: Hydrocortisone in induction; Drug: Idarubicin in induction-2; Drug: Fludarabine in induction-2; Drug: Ara-C in induction-2; Drug: G-CSF in induction-2; Drug: Dexamethasone in consolidation-1; Drug: Vincristrine in consolidation-1; Drug: Metotrexato in consolidation-1; Drug: PEG-ASP in consolidation-1; Drug: Dexamethasone in consolidation-2; Drug: ARA-C in consolidation-2; Drug: PEG-ASP in consolidation-2; Drug: Dexamethasone in consolidation-3; Drug: Vincristine in consolidation-3; Drug: Metotrexato in consolidation-3; Drug: PEG-ASP in consolidation-3; Procedure: allogeneic HSCT; Procedure: Allo HSCT with reduced-intensity conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Improve the results of the protocol ALL-AR-03 with modifications in the study methodology of residual disease: centralized, Biomed protocols and the cut-off - <0.01% - internationally accepted and changes in the induction and consolidation treatment, without altering the overall design
Measured: 2 years
Secondary outcomes (5)
Evaluate CR rate with addition of PEG-ASP in the induction phase
Measured: 2 years
Standarization of minimal residual disease
Determination of minimal residual disease in a central laboratory trying to homogenice the results
Measured: 2 years
To assess the toxic mortality
To assess whether the reduction of daunorubicin in induction and changes in the consolidation drugs reduce toxic mortality in patients in complete remission
Measured: 2 years
Assess the proportion of non-responders or slow responders
Measured: 2 years
Overall survival
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 posted29 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completion20 Nov 2019
- Study completion1 Dec 2019
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 Acute Lymphoblastic 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 418 participants (actual)
Sponsor and investigators
- Lead sponsor
- PETHEMA Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01540812
- Sponsor's protocol ID
- LAL-AR/2011
- Status last verified
- Mar 2020
- First submitted
- 23 Feb 2012
- Last updated
- 9 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ribera JM, Morgades M, Ciudad J, Montesinos P, Esteve J, Genesca E, Barba P, Ribera J, Garcia-Cadenas I, Moreno MJ, Martinez-Carballeira D, Torrent A, Martinez-Sanchez P, Monsalvo S, Gil C, Tormo M, Artola MT, Cervera M, Gonzalez-Campos J, Rodriguez C, Bermudez A, Novo A, Soria B, Coll R, Amigo ML, Lopez-Martinez A, Fernandez-Martin R, Serrano J, Mercadal S, Cladera A, Gimenez-Conca A, Penarrubia MJ, Abella E, Vall-Llovera F, Hernandez-Rivas JM, Garcia-Guinon A, Bergua JM, de Rueda B, Sanchez-Sanchez MJ, Serrano A, Calbacho M, Alonso N, Mendez-Sanchez JA, Garcia-Boyero R, Olivares M, Barrena S, Zamora L, Granada I, Lhermitte L, Feliu E, Orfao A. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia. Blood. 2021 Apr 8;137(14):1879-1894. doi: 10.1182/blood.2020007311.
PubMed 33150388
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Acute Lymphoblastic Leukemia HIGH RISK BCR / ABL NEGATIVE IN ADULTS
- ClinicalTrials.gov ID
- NCT01540812
- Acronym / sponsor ID
- LAL-AR/2011
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- Acute Lymphoblastic Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 418 participants (actual)
- Lead sponsor
- PETHEMA FoundationUniversity, hospital or other
- Study start
- Feb 2012 (actual)
- Primary completion
- 20 Nov 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 29 Feb 2012 (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.
Trial protocol intended the optimization of induction treatment with:
- Inclusion of PEG-ASP in induction and in the three blocks of consolidation.
- Reduction of the dose of daunorubicin, and recent studies have shown that the use of high doses of anthracyclines has not brought higher response rates or longer duration
- Replacing the poor cytological response at day 14 by the level of ER at the end of induction as a criterion to decide the further treatment (consolidation or second induction), so as to have only one criterion (the ER) throughout the study to decision making.
For another hand, reducing non-essential drugs consolidation blocks to try to reduce toxicity during it, and replace the ASP E. coli in induction and consolidation of PEG-ASP to ensure a more sustained asparagine depletion. Also, increasing the dose of methotrexate (3 to 5 g/m2) in patients with ALL-T, since there is recent evidence of a higher response rate with this strategy.
Performing an allo-HSCT early (after one cycle of consolidation) for patients with inadequate level of ER after two cycles of induction or in those patients who required two courses of induction and have obtained proper ER after the second.
Conducting studies of RD centrally by cytofluorometry following Euroflow consensus standards, to avoid bias in making treatment decisions
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud | – | Drug: Vincristine in induction, Drug: Daunorubicin in induction, Drug: Prednisone in induction, Drug: Metotrexato in induction, Drug: Cytarabine in induction, Drug: Hydrocortisone in induction, Drug: Idarubicin in induction-2, Drug: Fludarabine in induction-2, Drug: Ara-C in induction-2, Drug: G-CSF in induction-2, Drug: Dexamethasone in consolidation-1, Drug: Vincristrine in consolidation-1, Drug: Metotrexato in consolidation-1, Drug: PEG-ASP in consolidation-1, Drug: Dexamethasone in consolidation-2, Drug: ARA-C in consolidation-2, Drug: PEG-ASP in consolidation-2, Drug: Dexamethasone in consolidation-3, Drug: Vincristine in consolidation-3, Drug: Metotrexato in consolidation-3, Drug: PEG-ASP in consolidation-3, Procedure: allogeneic HSCT, Procedure: Allo HSCT with reduced-intensity conditioningVincristine in induction:5 mg/m2 i.v. days 1, 8, 15 and 22 in induction phase Daunorubicin in induction 45 mg/m2 i.v. days 1, 8, 15 and 22 Prednisone in induction: 60 mg/m2/ day, i.v. o p.o., days 1 to 14; 30 mg/m2/day, i.v. o p.o., days 15 to 21; 15 mg/m2/day i.v. o p.o., days 21 to 28 Metotrexato 12 mg days 1 and 22 (intrathecal) Cytarabine (ARA-C): 30 mg days 1 and 22 (intrathecal) Hydrocortisone: 20 mg days 1 and 22 (intrathecal) Idarubicin-induction 2 12 mg/m2, i.v., days 1, 3 and 5 Fludarabine in induction-2: Fludarabine 30 mg/m2, i.v., days, 1 to 5 |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- ALL patients
Key inclusion criteria (6 listed)
- ALL de novo high-risk criteria
- Age 15-55 years (55-60 years patients will be included at the discretion of the medical team that will attend)
- No prior treatment, except Emergency leukapheresis Emergency treatment of hyperleukocytosis with hydroxyurea Urgent cranial irradiation (one dose) for CNS leukostasis Mediastinal irradiation for urgent superior vena cava syndrome
- General condition suitable scale (ECOG 0-2), or> 2 if due to ALL
- Negative pregnancy test for women of childbearing age
Key exclusion criteria (14 listed)
- L3 type ALL or mature phenotype B (sIg +) or cytogenetic abnormalities characteristic of mature B-ALL (t (8; 14), t (2, 8), t (8; 22)). For these patients is available BURKIMAB protocol.
- LAL Ph (BCR-ABL) positive. For these patients have the protocol ALL-Ph-08 (if under 55) or LALOPh (if over 55).
- Lymphoid blast crisis of chronic myeloid leukemia
- Biphenotypic acute leukemia or bilinear according to the criteria of EGIL group
- Undifferentiated acute leukemias
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 |
|---|---|---|
| Vincristine in induction | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Daunorubicin in induction | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Prednisone in induction | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Metotrexato in induction | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Cytarabine in induction | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Hydrocortisone in induction | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Idarubicin in induction-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Fludarabine in induction-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Ara-C in induction-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| G-CSF in induction-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Dexamethasone in consolidation-1 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Vincristrine in consolidation-1 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Metotrexato in consolidation-1 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| PEG-ASP in consolidation-1 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Dexamethasone in consolidation-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| ARA-C in consolidation-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| PEG-ASP in consolidation-2 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Dexamethasone in consolidation-3 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Vincristine in consolidation-3 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Metotrexato in consolidation-3 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| PEG-ASP in consolidation-3 | Drug | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| allogeneic HSCT | Procedure or surgery | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
| Allo HSCT with reduced-intensity conditioning | Procedure or surgery | V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud |
Primary outcome
Overall response rate
Time frame: 2 years
Improve the results of the protocol ALL-AR-03 with modifications in the study methodology of residual disease: centralized, Biomed protocols and the cut-off - <0.01% - internationally accepted and changes in the induction and consolidation treatment, without altering the overall design
5 secondary outcomes
Evaluate CR rate with addition of PEG-ASP in the induction phase
Time frame: 2 years
Standarization of minimal residual disease
Time frame: 2 years
To assess the toxic mortality
Time frame: 2 years
Assess the proportion of non-responders or slow responders
Time frame: 2 years
Overall survival
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Derived from this study: PubMed 33150388Ribera JM, Morgades M, Ciudad J, Montesinos P, Esteve J, Genesca E, Barba P, Ribera J, Garcia-Cadenas I, Moreno MJ, Martinez-Carballeira D, Torrent A, Martinez-Sanchez P, Monsalvo S, Gil C, Tormo M, Artola MT, Cervera M, Gonzalez-Campos J, Rodriguez C, Bermudez A, Novo A, Soria B, Coll R, Amigo ML, Lopez-Martinez A, Fernandez-Martin R, Serrano J, Mercadal S, Cladera A, Gimenez-Conca A, Penarrubia MJ, Abella E, Vall-Llovera F, Hernandez-Rivas JM, Garcia-Guinon A, Bergua JM, de Rueda B, Sanchez-Sanchez MJ, Serrano A, Calbacho M, Alonso N, Mendez-Sanchez JA, Garcia-Boyero R, Olivares M, Barrena S, Zamora L, Granada I, Lhermitte L, Feliu E, Orfao A. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia. Blood. 2021 Apr 8;137(14):1879-1894. doi: 10.1182/blood.2020007311.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Lymphoblastic Leukemia, run by PETHEMA Foundation at 1 site in Spain.
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 14 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: finished, as of the sponsor's last update on 9 Mar 2020. 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 Spain. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: 2 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 NCT01540812, 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 9 Mar 2020.