A Study in Adults With Untreated Acute Lymphoblastic Leukemia

• ClinicalTrials.gov Identifier: NCT00136435
• Recruitment Status: Active, not recruiting
• First Posted: August 29, 2005
• Last Update Posted: March 20, 2020
• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Brigham and Women's Hospital; Massachusetts General Hospital; Queen Elizabeth II Health Sciences Centre
• Information provided by (Responsible Party): Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: August 25, 2005
• First Posted Date: August 29, 2005
• Last Update Posted Date: March 20, 2020
• Study Start Date: June 2002
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 14, 2005): To determine the feasibility, safety and efficacy of the high-risk pediatric treatment regimen in adult patients between the ages of 18 and 50 years
• Original Primary Outcome Measures (submitted: August 25, 2005): To determine the feasibility, safety and efficacy of the high-risk pediatric treatment regimen in adult patients between the ages of 18 and 50 years.

Current Secondary Outcome Measures (submitted: December 20, 2007)

• To determine the safety and optimal dosing of L-asparaginase during the intensification period [ Time Frame: 5 years ]
• to determine the effect of weekly E. coli L-asparaginase by evaluating serum asparaginase levels in all patients [ Time Frame: 5 years ]
• to determine the safety of individualized dosing of E. coli L-asparaginase based upon asparaginase levels [ Time Frame: 5 years ]
• to evaluate the outcome of patients based upon minimal residual disease status (MRD) after 28 days of multi-agent induction chemotherapy [ Time Frame: 5 years ]

Original Secondary Outcome Measures (submitted: August 25, 2005)

• To determine the safety and optimal dosing of L-asparaginase during the intensification period
• to determine the effect of weekly E. coli L-asparaginase by evaluating serum asparaginase levels in all patients
• to determine the safety of individualized dosing of E. coli L-asparaginase based upon asparaginase levels
• to evaluate the outcome of patients based upon minimal residual disease status(MRD) after 28 days of multi-agent induction chemotherapy.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study in Adults With Untreated Acute Lymphoblastic Leukemia
• Official Title: A Multicenter Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia: Testing Pharmacokinetically Individualized Doses of L-Asparaginase Following the DFCI Pediatric Consortium Protocol
• Brief Summary: The purpose of this study is to determine the safety and optimal dosing of L-asparaginase in adult patients with acute lymphoblastic leukemia (ALL) between the ages of 18 and 50 years.

Detailed Description

This study has four treatment phases: 1) induction, 2) central nervous system therapy, 3) intensification, and 4) continuation.

The induction phase lasts one month and eight drugs are used during this phase of treatment. The drugs are administered as follows:

• Prednisone; on days 1-28:
• Vincristine; on days 1, 8, 15, and 22:
• Doxorubicin; on days 1 and 2:
• Methotrexate; on day 3;
• Leucovorin; 36 hours after methotrexate:
• Asparaginase; on day 5:
• Intra-thecal Cytarabine; on days 1, 15, and 29:
• Intra-thecal Methotrexate/Hydrocortisone; on days 15 and 29

A bone marrow aspirate and biopsy will be obtained on day 15 and day 29 of induction therapy. If on day 29, the patients' bone marrow and peripheral blood counts are not in complete remission, then the patient may receive vincristine on days 29, 36 and 43. Bone marrow biopsy will be repeated weekly until complete remission is documented. If the patient does not achieve complete remission by day 49, they will be removed from the study.

Central nervous system (CNS) therapy begins immediately after the end of the induction therapy. This phase of treatment should last 3 weeks. Treatment includes a series of spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be performed over a two week period. Anti-leukemia drugs will also be given orally. The drugs given are as follows: Vincristine; on day 1: Doxorubicin; on day 1: 6-mercaptopurine (6-MP); on days 1-14: Intra-thecal Methotrexate/Cytarabine; 4 times over 2 weeks.

Radiation therapy (RT) will be delivered in 10 daily treatments during the CNS phase of therapy.

The intensification phase begins as soon as the CNS phase ends and lasts approximately 30 weeks. It consists of cycles of chemotherapy repeated every 3 weeks, along with asparaginase administered weekly. The drugs given are as follows: Vincristine; day 1: Dexamethasone; days 1-5: 6-MP; days 1-14: Doxorubicin; day 1: Asparaginase; weekly: Methotrexate; weekly: Intra-thecal Hydrocortisone/Methotrexate/cytarabine; every 18 weeks.

The continuation phase of treatment begins after the intensification phase. It consists of cycles of chemotherapy repeated every three weeks and will last until the patient is in remission for two years. The drugs given are: Vincristine; day 1 : Prednisone or Dexamethasone; days 1-5: 6-MP; days 1-14: Methotrexate; weekly: Intra-thecal Methotrexate/Cytarabine/Hydrocortisone: every 18 weeks.

During this study, blood tests will be performed at the start of therapy, at day 29 post induction and at the time of each intra-thecal therapy (every 18 weeks).

Bone marrow biopsy/aspirate will be done days 15 and 29 of induction, then every 6 months until completion.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Lymphoblastic Leukemia

Intervention

• Drug: prednisone
  Induction Phase: Given orally on days 1-28
• Drug: doxorubicin
  Induction Phaese: Given intravenously on day 1 and day 2 CNS Therapy: Given intravenously on day 1 Intensification: Given day 1 of each cycle
• Drug: vincristine

  Induction: Given intravenously on days 1, 8, 15, and 22. If complete remission not acheived, will be given on days 29, 36 and 43.

  CNS Therapy: Given intravenously on day 1. Intensification: Given intravenously on day 1 of each cycle. Continuation: Given intravenously on day 1 of each cycle

• Drug: methotrexate
  Induction: Given intravenously on day 3. CNS Therapy: Given intrathecally 4 times over two weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intravenously weekly and intrathecally every 18 weeks
• Drug: asparaginase
  Induction: Given into the muscle on day 5
• Drug: dexamethasone
  Intensification: Given orally on days 1-5 of each cycle
• Radiation: cranial radiation
  Given in 10 daily treatments during CNS therapy phase
• Drug: leucovorin
  Induction: Given intravenously or orally 36 hours after methotrexate
• Drug: cytarabine
  Induction: Given intrathecally days 1, 15, 29 CNS Therapy: Given intrathecally 4 times over 2 weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intrathecally every 18 weeks
  Other Name: Ara-C
• Drug: hydrocortisone
  Induction: Given intrathecally on days 15 and 29. Intensification: Given intrathecally every 18 weeks. Continuation: Given intrathecally every 18 weeks.
• Drug: 6-mercaptopurine (6-MP)
  CNS Therapy: Taken orally on days 1-14. Intensification: Taken orally on days 1-14. Continuation: Taken orally on days 1-14.
• Drug: e. coli L-asparaginase
  Intensification: Given in to the muscle weekly.

Study Arms

Only Arm for this study

Only Arm for this study

Interventions:

• Drug: prednisone
• Drug: doxorubicin
• Drug: vincristine
• Drug: methotrexate
• Drug: asparaginase
• Drug: dexamethasone
• Radiation: cranial radiation
• Drug: leucovorin
• Drug: cytarabine
• Drug: hydrocortisone
• Drug: 6-mercaptopurine (6-MP)
• Drug: e. coli L-asparaginase

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 20, 2007): 100
• Original Enrollment (submitted: August 25, 2005): 60
• Estimated Study Completion Date: January 2022
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have pathologically documented acute lymphoblastic leukemia, excluding mature B-cell ALL.

• No prior therapy for leukemia with the following exceptions:

  • up to one week of steroids;
  • emergent leukapheresis;
  • emergency treatment for hyperleukocytosis with hydroxyurea;
  • cranial RT for CNS leukostasis (one dose only);
  • emergent radiation therapy to the mediastinum.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Between the ages of 18 to 50 years.

Exclusion Criteria:

• Uncontrolled active infection.
• Pregnancy or nursing mothers.
• Prior history of pancreatitis.
• Prior history of a cerebrovascular accident or hemorrhage.
• Evidence of infection with the human immunodeficiency virus.
• Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely.
• The treating physician should consider all relevant medical and other considerations when deciding whether this protocol is appropriate for a particular patient.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00136435
• Other Study ID Numbers: 01-175
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute
• Study Sponsor: Dana-Farber Cancer Institute

Collaborators

• Brigham and Women's Hospital
• Massachusetts General Hospital
• Queen Elizabeth II Health Sciences Centre

Investigators

• Principal Investigator: Daniel J. DeAngelo, MD, PhD; Dana-Farber Cancer Institute

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: March 2020