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Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01005914
First received: October 30, 2009
Last updated: May 3, 2013
Last verified: May 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving pegaspargase together with combination chemotherapy and to see how well it works in treating patients with newly diagnosed acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
 Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: imatinib mesylate
Drug: methotrexate
Drug: methylprednisolone
Drug: pegaspargase
Drug: vincristine sulfate
Other: pharmacological study
 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Complete response rate after course 1 of pegaspargase when administered in combination with hyper-CVAD regimen [ Time Frame: After day 4 of treatment ] [ Designated as safety issue: No ]
    The complete response rate after 1A cycle of a PEG-Asparaginase and hyper-CVAD combination regimen will be estimated, and an exact 95% confidence interval will be computed using a binomial distribution.

  • Grade 3 and 4 toxicity associated with the combination of Peg-Asparaginase and hyper-CVAD which include: allergic reactions, elevated liver enzymes, hyperbilirubinemia, hyperglycemia, CNS thrombosis, and pancreatitis. [ Time Frame: The assessment of safety will be based mainly on the frequency of adverse events ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 2-year progression-free survival [ Time Frame: After completion of 8 cycles ] [ Designated as safety issue: No ]
  • Proportion of patients who achieve complete response or partial response after courses 1 and 2 [ Time Frame: An interim analysis of safety is planned after the enrollment of 15 evaluable patients. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At least every 6 months until death. ] [ Designated as safety issue: No ]
  • Rate of minimal residual disease [ Time Frame: End of cycles 1A and 1B ] [ Designated as safety issue: No ]
    Cycle 1A: Days 1 through 14 Cycle 1B: Days 1 through 8, after the first 14 days of cycle 1A

  • Half-life of pegaspargase [ Time Frame: The approximate t½ in adult patients is 5.73 days. The half-life is independent of the dose administered, disease status, renal or hepatic function, age, or gender. ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2009
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1

Drug:cyclophosphamide Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3

Drug:cytarabine Day 2 & 3: 3g/m2 IV over 2 hours q12 X 4

Drug:dexamethasone Day 1-4; 11-14: 40 mg daily

Drug:doxorubicin hydrochloride Day 4: 50 mg/m2 IV over 2 hours

Drug:imatinib mesylate 600 mg/day

Drug:methotrexate Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion

Drug: methylprednisolone Day 1-3: 50mg IV BID

Drug: pegaspargase Day 3/Day4: 2,500 IU/ m2 IV

Drug: vincristine sulfate Day 4 & 11: 2 mg IV

 Drug: cyclophosphamide
Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3
Drug: cytarabine
Day 2 & 3: 3g/m2 IV over 2 hours q12 X 4
Drug: dexamethasone
Day 1-4; 11-14: 40 mg daily
Drug: doxorubicin hydrochloride
Day 4: 50 mg/m2 IV over 2 hours
Drug: imatinib mesylate
600 mg/day
Other Name: Gleevec, Glivec
Drug: methotrexate
Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion
Drug: methylprednisolone
Day 1-3: 50mg IV BID
Drug: pegaspargase
Day 3/Day4: 2,500 IU/ m2 IV
Drug: vincristine sulfate
Day 4 & 11: 2 mg IV
Other: pharmacological study
Cycle 1A: pre-dose between Days 1 to 4 Cycle 1A: Days 11 or 12 (+/- 2 days) Cycle 1A: Days 18 or 19 (+/- 2 days) Cycle 1A: Days 25 or 26 (+/- 2 days) Cycle 1A: Days 32 or 33 (+/- 2 days)* Cycle 1B: pre-dose between Days 1 to 3 Cycle 1B: Days 1o or 11 (+/- 2 days) Cycle 1B: Days 17 or 18 (+/- 2 days) Cycle 1B: Days 24 or 25 (+/- 2 days) Cycle 1B: Days 31 or 32 (+/- 2 days)**

Detailed Description:

OBJECTIVES:

Primary

  • To estimate the complete response rate in patients with newly diagnosed acute lymphoblastic leukemia treated with pegaspargase in combination with hyper-CVAD regimen comprising cyclophosphamide, dexamethasone, vincristine sulfate, doxorubicin hydrochloride, methotrexate, and cytarabine.
  • To determine the safety and tolerability of this regimen in these patients.

Secondary

  • To evaluate the progression-free survival and overall survival of patients treated with this regimen.
  • To determine the half-life of pegaspargase when administered in combination with hyper-CVAD regimen.
  • To monitor the development of neutralizing antibodies to pegaspargase when administered in combination with hyper-CVAD regimen.
  • To assess minimal residual disease by flow cytometry at the end of courses 1A and 1B.

OUTLINE: This is a multicenter study.

  • Hyper-CVAD regimen (courses 1, 3, 5, and 7): Patients receive cyclophosphamide IV over 2-3 hours twice daily on days 1-3, dexamethasone IV on days 1-4 and 11-14, methotrexate intrathecally (IT) on day 2, doxorubicin hydrochloride IV over 2 hours and pegaspargase IV over 1-2 hours on day 4, vincristine sulfate IV on days 4 and 11, and cytarabine IT on day 8.
  • High-dose methotrexate/cytarabine regimen (courses 2, 4, 6, and 8): Patients receive methotrexate IV continuously over 24 hours on day 1, methylprednisolone IV twice daily on days 1-3, methotrexate IT on day 2, cytarabine IV over 2 hours twice daily on days 2 and 3, pegaspargase IV over 1-2 hours on day 3, and cytarabine IT on day 8.

Treatment repeats every 3-4 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients with Philadelphia chromosome-positive disease also receive oral imatinib mesylate daily beginning at diagnosis.

Patients who complete 8 courses of chemotherapy and are not candidates for hematopoietic stem cell transplantation receive maintenance therapy off study.

Blood samples are collected at baseline and periodically during study for pharmacokinetics and neutralizing antibody assays.

After completion of study therapy, patients are followed up every 6 months.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute lymphoblastic leukemia (ALL), including any of the following:

    • Precursor B-cell ALL

      • No mature B-cell (Burkitt) ALL
    • Precursor T-cell ALL
    • Philadelphia chromosome-positive ALL

  • Newly diagnosed disease based on bone marrow examination (unless there is a contraindication to having the test performed), meeting 1 of the following criteria:

    • > 20% blasts on bone marrow aspirate
    • Pathologic confirmation by bone marrow biopsy
    • WBC ≥ 10,000/μL with ≥ 20% circulating blasts
  • No documented CNS involvement with leukemia

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
  • Total bilirubin ≤ 2.0 times ULN
  • ALT and AST ≤ 2.0 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other active malignancy within the past 5 years except curatively treated basal cell and/or squamous cell skin cancer or carcinoma of the cervix
  • No severe pulmonary, renal, or hepatic disease not related to ALL

  • No cardiac dysfunction, including any of the following:

    • Myocardial infarction within the past 6 months
    • Reduced left ventricular function with an ejection fraction ≤ 50% as measured by MUGA scan or echocardiogram
    • Unstable angina
    • Unstable cardiac arrhythmias
    • NYHA class III or IV heart failure
    • Evidence of acute ischemia or active conduction system abnormalities by electrocardiography
  • No known or suspected HIV positivity
  • No concurrent severe and/or uncontrolled medical condition (e.g., uncontrolled diabetes, infection, hypertension) or psychiatric illness that, in the investigator's opinion, could potentially interfere with the completion of study treatment

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy for ALL

    • Hydroxyurea or one dose of IV vincristine sulfate allowed before study registration for patient convenience
  • Prior steroid therapy within the past 5 days allowed
  • More than 30 days since prior investigational agents
  • No other concurrent investigational or anticancer agents or therapies
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01005914

Locations
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Brandon Hayes-Lattin OHSU Knight Cancer Institute
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01005914     History of Changes
Other Study ID Numbers: CDR0000642363, P30CA069533, OHSU-4913, ENZON-OHSU-4913
Study First Received: October 30, 2009
Last Updated: May 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
T-cell adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
Pegaspargase
Imatinib
Dexamethasone
 Doxorubicin
Methylprednisolone Hemisuccinate
Prednisolone
Vincristine
Asparaginase
Dexamethasone acetate
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Dexamethasone 21-phosphate
Prednisolone hemisuccinate
Prednisolone phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on May 19, 2013