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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Sigma-Tau Research, Inc.
Duke University
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01920737
First received: August 7, 2013
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Daunorubicin
Drug: Vincristine
Drug: Prednisone
Drug: PEG-Asparaginase
Drug: Methotrexate
Drug: 6-MP (6-Mercaptopurine)
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Leucovorin
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Novel "Pediatric-Inspired" Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • rate of molecular remission [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    i.e. minimal residual disease (MRD) negative status, as assessed by PCR and flow cytometry in the bone marrow after phase I induction.


Secondary Outcome Measures:
  • complete remission (CR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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.
    • 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.

  • overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    OS will be calculated from the start of induction therapy to death or last follow-up.

  • event-free survival (EFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    EFS survival will be calculated from the start of induction therapy to relapse (molecular or clinical), death, or last follow-up.

  • disease free survival (DFS) rates [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    DFS will be calculated from the time of clinical CR (or better) to relapse (molecular or clinical), death, or last follow-up.

  • minimal residual disease (MRD) status [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 39
Study Start Date: August 2013
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Leukemia Patients

The treatment plan has 6 treatment cycles. The cycle names are listed in the following order:

Induction Phase I - Induction Phase II - Intensification I - Re-induction I - Intensification II - Re-induction II Each cycle is given over a period of 4-6 weeks and the interval between them can range between 1-3 weeks. Based the patients medical condition, the doctor may decide to change the timing of the drugs, the interval between the drugs in a cycle, or the interval between the cycles. After receiving all cycles you will continue with a 36 months treatment part that is called Maintenance.

Drug: Daunorubicin
In the event of a shortage of daunorubicin, doxorubicin may be used as a substitute.
Drug: Vincristine Drug: Prednisone Drug: PEG-Asparaginase Drug: Methotrexate Drug: 6-MP (6-Mercaptopurine) Drug: Cyclophosphamide Drug: Cytarabine Drug: Leucovorin Drug: Dexamethasone

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 lymphoblastic lymphoma confirmed by conventional immature T-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.

Exclusion Criteria:

  • Previous treatment for ALL, expect 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01920737

Contacts
Contact: Dan Douer, MD 212-639-2471
Contact: Jae Park, MD 212-639-4048

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Dan Douer, MD    212-639-2471      
Contact: Jae Park, MD    212-639-4048      
Principal Investigator: Dan Douer, MD         
Weill Cornell Medical Center Recruiting
New York, New York, United States
Contact: Ellen Ritchie, MD         
Principal Investigator: Ellen Ritchie, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27701
Principal Investigator: Arati Rao, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Sigma-Tau Research, Inc.
Duke University
Weill Medical College of Cornell University
Investigators
Principal Investigator: Dan Douer, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01920737     History of Changes
Other Study ID Numbers: 12-266
Study First Received: August 7, 2013
Last Updated: August 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
ALL
Bone Marrow
Ph Negative
Daunorubicin
Vincristine
Prednisone
PEG-Asparaginase
Methotrexate
16-MP (6-Mercaptopurine)
Cyclophosphamide
Cytarabine
Leucovorin
Dexamethasone
12-266

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
6-Mercaptopurine
Asparaginase
BB 1101
Cyclophosphamide
Cytarabine
Daunorubicin
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Methotrexate
Pegaspargase
Prednisone
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimetabolites

ClinicalTrials.gov processed this record on October 23, 2014