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ALLPhase 2PONALFILNCT02776605

Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia

A Phase 2 study testing Prednisone, Vincristine and Daunorubicin in people with ALL, run by PETHEMA Foundation at 10 sites in Spain.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

Evaluate the response (complete hematologic response [CHR], complete cytogenetic response [CCyR], major molecular response [MMR] and complete molecular response [CMR] of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
ALL
What is being tested?
Prednisone, Vincristine and Daunorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
10 sitesSpain
Study dates
Jun 2016to Aug 2023
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 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Age 18-55 yr.
  • De novo Ph+ (BCR-ABL)ALL
  • ECOG score ≤2 unless due to ALL
  • Absence of significant liver disease, as defined by the following criteria: total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 x ULN if leukemic involvement of the liver is present, and aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 x ULN if leukemic involvement of the liver is present.
  • Adequate pancreatic function as defined by serum lipase and amylase ≤1.5 × ULN.
  • No history of dyslipidemia, hypertension, thrombotic events or cardiac disease.
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  • For females of childbearing potential, a negative pregnancy test must be documented prior to randomization. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from randomization through 4 months after the end of treatment.
  • informed consent signed, according to national regulation
  • Patients aged between 56 and 60 years may be selected who could be included in the study with the authorization of the Coordinating Investigator with the consolidation treatment modified as follows:
  • Mercaptopurine (MP): 50 mg / m2, PO on days 1 to 7, 28 to 35 and 56 to 63 MTX: 0.75 g / m2, IV (continuous infusion 24 h) on days 1, 28 and 56 ARA-C: 500 mg / m2 / 12 h, IV, days 14-15 and 42-43 TIT (MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), days 1, 28 and 56 Ponatinib 30 mg / d PO, from day 1 to 7 days before HSCT

Who cannot join

  • Lymphoid blast crisis of CML,
  • WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG).
  • Active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubin ≥ 1.5 x ULN.
  • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.
  • History of alcohol abuse.
  • Ongoing or active infections.
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  • Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
  • Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to: Any history of myocardial infarction, stroke, or revascularization, Unstable angina or transient ischemic attack within 6 months prior to enrollment Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards History of clinically significant (as determined by the treating physician) atrial arrhythmia Any history of ventricular arrhythmia Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism.
  • Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
  • Taking medications that are known to be associated with torsades de pointes.
  • Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
  • Creatinine levels > 2.5mg/dl or glomerular filtration rate (GFR) < 20 ml/min or proteinuria >3.5 g/day.
  • Gastrointestinal (GI) function impairment, or a GI disease that may significantly alter the absorption of study drugs.
  • Patients who are currently receiving treatment with any of the medications with potential to prolong QT interval (listed in Appendix 4) if the medications cannot be either discontinued or switched to a different medication prior to starting study drug.
  • Patients who have received any investigational drug ≤ 4 weeks.
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs. prior to administration of Ponatinib). Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 4 months following discontinuation of study drugs.
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Patients unwilling or unable to comply with the protocol

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • Hospital Germans Trias i Pujol

    Badalona

  • Hospital Clinic

    Barcelona, 08036

  • Hospital 12 de Octubre

    Madrid

  • Hospital Virgen de la Victoria

    Málaga

  • Hospital Clinico Universitario de Salamanca

    Salamanca

  • Hospital Marques de Valdecilla

    Santander

  • C H Santiago de Compostela

    Santiago de Compostela

  • Hospital Virgen del Rocio

    Seville

  • Hospital Clinico de Valencia

    Valencia

  • Hospital La Fe

    Valencia

Other trials in Spain

About this study

Official title: Concurrent Ponatinib With Chemotherapy for Young Adults With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Evaluate the response (complete hematologic response [CHR], complete cytogenetic response [CCyR], major molecular response [MMR] and complete molecular response [CMR] of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL.

All patients are treated with:

Read more

Pre-phase (maximum 7 days, -7 to -1):

Prednisone 60 mg/m2/day IV over 7 days (-7 a -1) and triple intrathecal therapy (TIT) (Methotrexate [MTX]: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg). 2. Induction (day 1 to day 28 or up to hematological recovery) Vincristine (VCR): 1.5 mg/m2 (maximum 2 mg) IV days 1, 8, 15 and 22. Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15 and 22. Prednisone (PDN): 60 mg/m2/day, IV or PO, days 1 to 27. Ponatinib 30 mg, PO from day 1 to consolidation. TIT, days 1 and 22. 3. Consolidation (day 1 to day 63) Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7, 28 to 35 and 56 to 63. MTX: 1,5 g/m2, IV (24 h continuous infusion) days 1, 28 and 56. VP-16: 100 mg/m2/12 h, IV, days 14 and 42. ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43. TIT (MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), , days 1, 28 and 56. Ponatinib 30 mg/d PO, from day 1 to 15 days before HSCT. 4. HSCT (performed ideally within 1 month from the end of consolidation). AlloHSCT preferred over autoHSCT (autoHSCT only indicated if alloHSCT not feasible). Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI) whenever possible. 5. Post HSCT therapy After alloHSCT. Frequent monitoring of MRD (every month). I After autoHSCT: Frequent monitoring of MRD (every month).

Read the detailed description

Objectives Primary

  1. To evaluate the response (complete hematologic response [CHR], complete cytogenetic response [CCyR], major molecular response [MMR] and complete molecular response [CMR] of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL.
  2. To evaluate the event free survival (EFS) of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL. Secondary
  • To evaluate the rate of patients receiving an allogeneic hematopoietic stem cell transplant (alloHSCT) in first CR
  • To evaluate the frequency of MMR and CMR at the time of alloHSCT
  • To evaluate the transplant-related mortality (TRM)
  • To evaluate the CR duration and overall survival (OS) of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL.
  • To evaluate the outcome measures (CR duration, OS and EFS) in context of those observed in the PETHEMA ALL Ph08 trial.
  • To observe the type and number of BCR-ABL kinase domain mutations developing during and after the study.
  • To evaluate side effects, adverse events (AE) and serious AE (SAE).

Interventions:

  1. Pre-phase (maximum 7 days, -7 to -1): Prednisone 60 mg/m2/day IV over 7 days (-7 a -1) and triple intrathecal therapy (TIT) (Methotrexate [MTX]: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg).
  2. Induction (day 1 to day 28 or up to hematological recovery) Vincristine (VCR): 1.5 mg/m2 (maximum 2 mg) IV days 1, 8, 15 and 22. Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15 and 22. Prednisone (PDN): 60 mg/m2/day, IV or PO, days 1 to 27. Ponatinib 30 mg, PO from day 1 to consolidation. TIT, days 1 and 22.
  3. Consolidation (day 1 to day 63) Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7, 28 to 35 and 56 to 63. MTX: 1,5 g/m2, IV (24 h continuous infusion) days 1, 28 and 56. VP-16: 100 mg/m2/12 h, IV, days 14 and 42. ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43. TIT (MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), , days 1, 28 and 56. Ponatinib 30 mg/d PO, from day 1 to 15 days before HSCT.
  4. HSCT (performed ideally within 1 month from the end of consolidation). AlloHSCT preferred over autoHSCT (autoHSCT only indicated if alloHSCT not feasible). Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI) whenever possible.
  5. Post HSCT therapy After alloHSCT. Frequent monitoring of MRD (every month). If MRD negative: no therapy. If MRD positive, Ponatinib 30 mg/d, po, until 2 yr. after HSCT. The ponatinib dose will be reduced to 15 mg/d in the second year in patients with sustained molecular response. After autoHSCT: Frequent monitoring of MRD (every month). All patients will receive Ponatinib: 30 mg/d, PO, mercaptopurine, (40 mg/m2/d, PO) and methotrexate (15 mg/m2/week, IM), during the first year after HSCT. The ponatinib dose will be reduced to 15 mg/d in the second year in patients with sustained molecular response.
Conditions
ALL
Being tested
Prednisone, Vincristine, Daunorubicin, Ponatinib, Mercaptopurine

What participants receive

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

  • PrednisoneDrug

    Prednisone 60 mg/m2/day IV over 7 days (-7 a -1) and triple intrathecal therapy (TIT)

  • VincristineDrug

    Vincristine (VCR): 1.5 mg/m2 (maximum 2 mg) IV days 1, 8, 15 and 22.

  • DaunorubicinDrug

    Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15 and 22.

  • PrednisoneDrug

    Prednisone (PDN): 60 mg/m2/day, IV or PO, days 1 to 27.

  • PonatinibDrug

    Ponatinib 30 mg, PO from day 1 to consolidation

  • MercaptopurineDrug

    Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7, 28 to 35 and 56 to 63.

  • MethotrexateDrug

    MTX: 1,5 g/m2, IV (24 h continuous infusion) days 1, 28 and 56

  • VP-16Drug

    VP-16: 100 mg/m2/12 h, IV, days 14 and 42

  • ARA-C:Drug

    ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43.

  • TITDrug

    TIT (MTX: 12 mg, ARA-C: 30 mg, hydrocortisone: 20 mg), , days 1, 28 and 56.

  • PonatinibDrug

    Ponatinib 30 mg/d PO, from day 1 to 15 days before HSCT.

  • Autologous transplantationProcedure or surgery

    Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI) whenever possible and autologous transplantation

  • Allo transplantationProcedure or surgery

    Myeloablative conditioning with cyclophosphamide and total body irradiation (TBI) whenever possible and allo transplantation

Study groups in NCT02776605
Study groupRoleWhat they receive
PonatinibExperimental1. Pre-phase (maximum 7 days, -7 to -1) with Prednisone and triple intrathecal therapy (TIT) 2. Induction (day 1 to day 28 or up to hematological recovery) Vincristine (VCR): 1.5 mg/m2 IV days 1, 8, 15 and 22. Daunorubicin (DNR): 45 mg/m2 IV days 1, 8, 15 and 22. Prednisone (PDN): 60 mg/m2/day, IV or PO, days 1 to 27. Ponatinib 30 mg, PO from day 1 to consolidation. TIT, days 1 and 22. 3. Consolidation Mercaptopurine (MP): 50 mg/m2, PO days 1 to 7, 28 to 35 and 56 to 63. MTX: 1,5 g/m2, IV days 1, 28 and 56. VP-16: 100 mg/m2/12 h, IV, days 14 and 42. ARA-C: 1000 mg/m2/12 h, IV, days 14-15 and 42-43. TIT days 1, 28 and 56. Ponatinib 30 mg/d PO, from day 1 to day 7 before HSCT". 4. HSCT (performed ideally within 1 month from the end of consolidation). 5. Post HSCT therapy (MRD monitoring)
Receives: Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: Ponatinib; Drug: Mercaptopurine; Drug: Methotrexate; Drug: VP-16; Drug: ARA-C:; Drug: TIT; Procedure: Autologous transplantation; Procedure: Allo transplantation

What is being measured

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

  1. Overall response

    To evaluate the response (complete hematologic response [CHR], complete cytogenetic response [CCyR], major molecular response [MMR] and complete molecular response [CMR] of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL.

    Measured: 2 years

  2. Event free survival

    To evaluate the event free survival (EFS) of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL

    Measured: 2 years

Timeline

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

  1. First posted18 May 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion5 Aug 2020
  4. Study completionAug 2023 (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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02776605
Sponsor's protocol ID
PONALFIL
Acronym
PONALFIL
Status last verified
Feb 2022
First submitted
16 May 2016
Last updated
18 Feb 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Ribera JM, Garcia-Calduch O, Ribera J, Montesinos P, Cano-Ferri I, Martinez P, Esteve J, Esteban D, Garcia-Fortes M, Alonso N, Gonzalez-Campos J, Bermudez A, Torrent A, Genesca E, Mercadal S, Martinez-Lopez J, Garcia-Sanz R. Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Adv. 2022 Sep 27;6(18):5395-5402. doi: 10.1182/bloodadvances.2022007764.

    PubMed 35675590

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Prednisone, Vincristine and Daunorubicin in people with ALL, run by PETHEMA Foundation at 10 sites 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 10 inclusion and 19 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 18 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites 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.

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?

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 (time frame: 2 years). The study lists 2 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 NCT02776605, 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 18 Feb 2022.

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PONALFIL Clinical Trial NCT02776605 | AzTrials