40 Yaş ve Üzeri Yeni Tanı Konmuş Philadelphia Kromozomu Pozitif Akut Lenfoblastik Lösemi Hastalarında Remisyon İndüksiyon Tedavisinde Dasatinib ve Dexamethasone Kombinasyonuna Ruxolitinib Eklenmesi

Sade dilde özet

Bu çalışma, remisyon (hastalığın gerilemesi) sağlamaya yönelik tedavide Dasatinib ve Dexamethasone kombinasyonuna Ruxolitinib eklenmesini, Philadelphia kromozomu pozitif akut lenfoblastik lösemi (acute lymphoblastic leukemia, ALL) hastalarında incelemiştir. Çalışmaya, 18 yaş ve üzeri, Philadelphia kromozomu pozitifliği doğrulanmış hastalar dahil edilmiştir. Çalışma Faz 1 aşamasında yürütülmekte; şu an katılımcı almamakta ancak devam etmektedir (active, not recruiting).

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Faz 1 (Phase 1)

Durum

Devam ediyor, katılım kapalı

Sponsor

Memorial Sloan Kettering Cancer Center

Müdahale

Ruxolitinib, Dasatinib, Dexamethasone

Başlangıç

29.06.2015

Tahmini bitiş

01.06.2027

Ülkeler

United States

İlgili genler

Merkezler

• New York, United States

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

Inclusion Criteria:

* Patient able to give informed consent.
* Patients \>/= 18 years with the following disease will be eligible

  * Newly diagnosed Ph+ ALL, previously untreated, except for the below allowances
  * Previously received HpyerCVAD cycle 1A+/- cycle 1B
  * Previously received Induction Phase 1 +/- Induction Phase II of BFM-modeled (Pediatric of Pediatric-Inspired) ALL regimen
  * Previously received other representative (modified from HyperCVAD, BFM, or AML-like) ALL induction course, including ABL TKI plus corticosteroid.
  * If the patient has received any of the above prior therapy, they may be enrolled, regardless of remission status.
  * Relapsed PH+ ALL, with no prior exposure to dasatinib and without known ABL kinase mutations predited to be resistant to dasatibin (e.g. L248R, L248V, Q252H, E255K, V299L, T315A, T315I, F317C, F317L, F317S, F317V)
  * Relapsed or refractory Ph-like ALL without prior exposure to dasatibin and with mutations or rearrangements of genes conferring sensitivity to dasatibin (ABL, CSF1R, PDGFRB) or ruxolitinib (CRLF2, JAK3, EPOR, TSLP)
  * Newly diagnosed or relapsed CML in lymphoid blast crisis
* Confirmation of Philadelphia chromosome positivity by cytogenetics (karyotype/FISH) and/or molecular tests (BCR-ABL1 transcripts)
* Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself
* ECOG performance status ≤ 2
* Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and for at least 4 months following treatment on study

Exclusion Criteria:

* Ph-negative ALL
* Patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis
* Mature B-cell (Burkitt's) ALL
* Serum creatinine \> 1.5x ULN and calculated creatinine clearance, based on a 24-hour urine collection, \< 30 mL/min--unless related to ALL/tumor lysis syndrome and able to be corrected
* Direct Bilirubin \> 2x ULN; AST/ALT \> 10x ULN, unless related to ALL liver infiltration.
* Pregnant women or women who are breast-feeding
* Patients with HIV, Hepatitis B, or Hepatitis C
* Pre-treatment QTcF \> 480 msecs
* A "washout" period of at least 14 days from last previous cytotoxic chemotherapy will be required prior to starting treatment on this protocol. No "washout" period will be required for previous bcr-abl TKI therapy given with the aforementioned previous chemotherapy cycles. Hydroxyurea and corticosteroids may be given as bridge therapy up until 24 hours prior to initiating protocol treatment.
* Active malignancy requiring treatment other than ALL within two years prior to start of treatment, with the exception of basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, localized prostate cancer, or DCIS or LCIS of the breast
* Active, uncontrolled infection, any other concurrent disease, or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
* Unable to tolerate anti-viral and anti- Pneumocystis jirovecii prophylaxis while on pre-phase and remission induction therapy
* Unable to tolerate gastrointestinal prophylaxis therapy with sucralfate while on pre-phase and remission induction therapy. Or severe pre-existing GI disorder that requires PPI or H2 receptor antagonist therapy be uninterrupted