Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

Studienbeginn:
Juli 2023

Letztes Update:
29.09.2023

Wirkstoff:
Imatinib, Ponatinib, Blinatumomab

Indikation (Clinical Trials):
Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid, Philadelphia Chromosome

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Goethe University

Collaborator:
Deutsche Leukämie- & Lymphom-Hilfe, German Federal Ministry of Education and Research,

Studienleiter

Nicola Goekbuget, MD
Principal Investigator
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany

Fabian Lang, MD
Principal Investigator
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany

Heike Pfeifer, MD
Principal Investigator
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany

Kontakt

Nicola Goekbuget, MD
Kontakt:
Phone: 0049-6963016365
E-Mail: goekbuget@em.uni-frankfurt.de» Kontaktdaten anzeigen

Fabian Lang, MD
Kontakt:
Phone: 0049-69630183044
E-Mail: fabian.lang@kgu.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Department of Medicine, Hematology and Oncology, Goethe University Hospital Frankfurt
60580 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Nicola Goekbuget, MD
Phone: 0049-6963016365
E-Mail: goekbuget@em.uni-frankfurt.de

Fabian Lang, MD
Phone: 0049-69630183044
E-Mail: fabian.lang@kgu.de» Ansprechpartner anzeigen

Studien-Informationen

Brief Summary:

The current Standard of Care (SoC) in younger patients with Ph+ ALL is Imatinib in

combination with low-dose chemotherapy, change of TKI in case of persistent MRD above 10-3

after consolidation I and indication for stem cell transplantation.

The EVOLVE trial aims to answer three questions challenging the current SoC:

Use of Ponatinib compared to Imatinib both in combination with low-dose chemotherapy and

consolidation I (randomization I).

In MRD good responders: Omit end of therapy in primary care and indication for SCT but

continue therapy with TKI, chemotherapy and Blinatumomab as additional antileukemic compound

(randomization II).

In MRD poor responders: Omit indication for TKI change but give instead Blinatumomab followed

by end of therapy in primary care and indication for SCT (non-randomized).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Male or female patients >= 18 years, <=65 years

- Philadelphia chromosome or BCR-ABL1 positive ALL

- Not previously treated except with corticosteroids ≤ 7 days, standard GMALL prephase

with dexamethasone and cyclophosphamide including intrathecal therapy, hydroxyurea, a

single dose vincristine or other cytostatic drugs and start of standard induction for

Ph-positive ALL (1 dose vincristine, 1 dose of Rituximab, 2 doses dexamethasone and up

to 5 days Imatinib)

- ECOG performance status ≤2

- Signed written inform consent

- Molecular evaluation for BCR-ABL1 performed

- Negative pregnancy test in women of childbearing potential

- Woman of childbearing potential willing to use 2 highly effective methods of

contraception while receiving study treatment and for an additional 3 months after the

last dose of study treatment (Pearl-Index <1%). Male who has a female partner of

childbearing potential willing to use 2 highly effective forms of contraception while

receiving study treatment and for at least an additional 3 months after the last dose

of study treatment (Pearl-Index <1%).

- Normal serum levels > LLN (lower limit of normal) of potassium and magnesium, or

corrected to within normal limits with supplements, prior to the first dose of study

medication

- Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value must be

considered not clinically significant and not associated with risk factors for acute

pancreatitis

- Normal QTcF interval ≤450 ms for males and ≤470 ms for females

- Signed and dated written informed consent is available

- Participation in the registry of the German Multicenter Study Group for Adult ALL

(GMALL)

Exclusion Criteria:

- History of malignancy other than ALL diagnosed within 5 years (yrs) prior to start of

protocol-specified therapy with defined exceptions

- Contraindications against the use of Imatinib, Ponatinib, chemotherapy or Blinatumomab

- Patient previously treated with tyrosine kinase inhibitors

- Nursing women

- Known impaired cardiac function, including any of the following: as detailed in

protocol

- Symptomatic peripheral vascular disease

- Any history of ischemic stroke or transient ischemic attacks (TIAs)

- Uncontrolled hypertriglyceridaemia

- History or presence of clinically relevant CNS pathology as detailed in protocol

- History or active relevant autoimmune disease

- Known hypersensitivity to immunoglobulins or to any other component of the study drug

formulation

- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not

mandatory) or active infection with Hepatitis B or C

- History of pancreatitis within 6 months previous to start of treatment within the

trial

- Treatment with any other investigational agent or participating in another trial

within 30 days prior to entering this study

- Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional

upper limit of normal or > 5 times ULN if considered due to leukemia

- Total bilirubin > 1.5-fold the institutional upper limit unless considered to be due

to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht

- Concurrent severe diseases which exclude the administration of therapy e.g. severe,

uncontrolled acute or chronic infections

- Inability to understand and/or unwillingness to sign a written informed consent

Studien-Rationale

Primary outcome:

1. OS in MolCR patients treated with TKI-Chemo-Blina versus (vs) EOT with indication for SCT (Standard of Care) (Time Frame - up to 4 years from randomization I):
Probability of overall survival up to 4 years from randomization I in patients with mo-lecular remission after consolidation 1 comparing a combination treatment of TKI, Blina-tumomab and chemotherapy versus EOT with indication for SCT

Secondary outcome:

1. Rate of molecular complete remission at week 11 after consolidation (Time Frame - week 11 after consolidation):
Rate of molecular complete remission at week 11 after consolidation with chemotherapy in combination with Ponatinb versus Imatinib

Studien-Arme

Active Comparator: A: Imatinib + low dose chemotherapy
Imatinib 600mg QD + low dose chemotherapy induction and consolidation I (Standard Arm of Randomization I)
Experimental: B: Ponatinib + low dose chemotherapy
Ponatinib 45mg QD (reduction to 30mg QD after Induction) + low dose chemotherapy induction and consolidation I (Experimental Arm of Randomization I)
Active Comparator: C: Molecular CR: End of therapy with indication for SCT
Molecular CR: End of therapy with indication for SCT (Standard Arm of Randomization II)
Experimental: D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and Blinatumomab
Molecular CR: No end of therapy with indication for SCT but and continuation with Imatinib/Ponatinib (per Randomization I), chemotherapy and Blinatumomab (Experimental Arm of Randomization II)
Experimental: E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of Blina
Molecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm)

Geprüfte Regime

Imatinib:
Imatinib 600mg QD plus Chemotherapy
Ponatinib:
Ponatinib 45 mg QD plus chemotherapy
Blinatumomab:
Patients with molecular failure or intermediate response receive one cycle Blinatumomab before SCT; Patients with molecular CR randomized to the experimental arm receive 3 cycles Blinatumomab + chemotherapy
Indication for stem cell transplantation:
Patients with molecular CR randomized to the standard arm have an indication for SCT; patients with molecular failure or intermediate response have an indication for SCT. SCT is not part of the trial.

Quelle: ClinicalTrials.gov

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