Clinical trial NCT01920737: A Novel "Pediatric-Inspired" Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia
Official title: A Novel "Pediatric-Inspired" Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Leukemia
Keywords: ALL
Bone Marrow
Ph Negative
Daunorubicin
Vincristine
Prednisone
PEG-Asparaginase
Methotrexate
16-MP (6-Mercaptopurine)
Cyclophosphamide
Cytarabine
Leucovorin
Dexamethasone
12-266
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Shire
name: Duke University
name: Weill Medical College of Cornell University
name: Lehigh Valley Health Network
First posted: 2013-08-12
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to find out whether the combination of chemotherapy drugs that are routinely used in children with ALL, will be safe and effective in treating adult patients with ALL. The standard treatment for adults with ALL consists of many chemotherapy drugs that are given in different combinations and in several steps. In adult ALL there is no standard which drugs to give and how to combine them. Some leukemias have a chromosome abnormality called Philadelphia chromosome (also called Ph Positive) and some leukemias do not (called Ph Negative). In this study we want to see whether this combination of chemotherapy drugs will be safe and effective in treating adult patients with Ph Negative ALL.


Eligibility criteria: Inclusion Criteria:

* Previously untreated Ph negative precursor B-cell or T-cell ALL confirmed by conventional flow cytometry or immunohistochemical stain Patients who have untreated B-cell or T-cell ALL confirmed by conventional flow cytometry or immunohistochemical stain, but Ph status is unknown, may also enroll.
* Patients with T-cell or B cell lymphoblastic lymphoma confirmed by conventional immature T- or pre B cell markers even if the bone marrow is not involved are also eligible
* Age 18 - 60 years
* ECOG performance status of 0-2
* Adequate renal function as demonstrated by a serum creatinine ≤ 2.0 mg/dl or a creatinine clearance of \> 60 ml/min.
* Adequate hepatic function as demonstrated by a total bilirubin \< 2.0 mg/dl (unless attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 4 times the upper limit of normal (unless clinically considered to be related to liver involvement with leukemia
* Normal cardiac function as demonstrated by a left ventricular ejection fraction ≥ 50% on echocardiogram or MUGA scan
* Negative serum pregnancy test in women of childbearing potential
* Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and at least 4 months after treatment is finished.
* Patients with central nervous system involvement by ALL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice. For patients with CNS disease, dexamethasone may be temporarily administered instead of prednisone to reduce CNS pressure, at the discretion of the treating physician and after discussion with the MSK PI. Once dexamethasone is no longer needed, prednisone should be given as per protocol for 28 days.

Exclusion Criteria:

* Previous treatment for ALL, except for prior steroids and/or hydroxyurea
* Patients known to have Philadelphia (Ph)+ ALL are not eligible. Leukemia cell samples will be obtained from all patients enrolled before starting protocol treatment and submitted for Philadelphia chromosome testing by either karyotyping, or for bcr/abl1 translocation by FISH or by PCR for bcr/abl1. Patients who are later found to have Ph+ ALL should have treatment on this trial discontinued and will not be considered in the evaluation
* Lymphoid blastic crisis of chronic myelogenous leukemia
* Mature B-cell (Burkitt's) ALL
* Active serious infections not controlled by antibiotics
* Pregnant women or women who are breast-feeding
* Concurrent active malignancy requiring immediate therapy
* Clinically significant cardiac disease (NY Heart Association Class III or IV), including chronic arrhythmias, or pulmonary disease
* Known HIV positive status
* Other serious or life-threatening conditions deemed unacceptable by the principal investigator

Primary outcomes:
measure: rate of molecular remission
timeFrame: 1 year
Secondary outcomes:
measure: complete remission (CR)
timeFrame: 1 year
measure: overall survival (OS)
timeFrame: 1 year
measure: event-free survival (EFS)
timeFrame: 1 year
measure: disease free survival (DFS) rates
timeFrame: 1 year
measure: minimal residual disease (MRD) status
timeFrame: 1 year
measure: safety
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jae Park, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Geyer MB, Ritchie EK, Rao AV, Vemuri S, Flynn J, Hsu M, Devlin SM, Roshal M, Gao Q, Shukla M, Salcedo JM, Maslak P, Tallman MS, Douer D, Park JH. Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia. Haematologica. 2021 Aug 1;106(8):2086-2094. doi: 10.3324/haematol.2020.251686.