A Novel "Pediatric-Inspired" Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia

Leukemia Clinical Trial

Official title:

A Novel "Pediatric-Inspired" Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01920737
• Other study ID #: 12-266
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 2013
• Est. completion date: August 2024

Study information

• Verified date: October 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Daunorubicin
In the event of a shortage of daunorubicin, doxorubicin may be used as a substitute.
• Vincristine

• Prednisone

• PEG-Asparaginase

• Methotrexate

• 6-MP (6-Mercaptopurine)

• Cyclophosphamide

• Cytarabine

• Leucovorin

• Dexamethasone

Other:
• Blood draw

Device:
• CT/PET scans
PET or CT scan every 6 months for 3 years

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical Center	New York	New York

Sponsors (5)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Duke University, Lehigh Valley Health Network, Shire, Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of molecular remission	i.e. minimal residual disease (MRD) negative status, as assessed by PCR and flow cytometry in the bone marrow after phase I induction.	1 year
Secondary	complete remission (CR)	All three criteria must be met for clinical complete remission: Peripheral Blood Counts. The absolute neutrophil count should be =1,000/µl (sustained without growth factor support), and platelet count should be =100,000/µl (without transfusions), and no circulating blasts. After Induction remission assessment, blood counts are considered recovered at ANC = 1,000 and PLT =75,000.; Bone Marrow Aspirate. Bone marrow cellularity should be approximate normal with evidence of maturation of all cell lineages and should contain <5% blasts.; Extramedullary Leukemia, such as CNS or soft tissue involvement, must not be present. If the patient had CNS involvement by ALL at the time of starting the study, the CNS involvement should be re-examined and interval determined by the treating physicians in order to determine if clinical complete remission	1 year
Secondary	overall survival (OS)	OS will be calculated from the start of induction therapy to death or last follow-up.	1 year
Secondary	event-free survival (EFS)	EFS survival will be calculated from the start of induction therapy to relapse (molecular or clinical), death, or last follow-up.	1 year
Secondary	disease free survival (DFS) rates	DFS will be calculated from the time of clinical CR (or better) to relapse (molecular or clinical), death, or last follow-up.	1 year
Secondary	minimal residual disease (MRD) status	Molecular relapse is defined as the conversion of RT-PCR from MRD negative to MRD positive on two consecutive tests performed on bone marrow at least one week apart, while still meeting criteria for clinical CR.	1 year
Secondary	safety	Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 will be tabulated.	1 year

External Links

•   Memorial Sloan Kettering Cancer Center