ALL Adult Consortium Trial: Adult ALL Trial

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Massachusetts General Hospital
Children's Hospital Boston
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00476190
First received: May 18, 2007
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to determine the safety and effectiveness of a multi-drug chemotherapy regimen in adult patients with Acute Lymphoblastic Leukemia (ALL). We will use a regimen that is often used in pediatric patients and we will add drugs called PEG-asparaginase and E. coli asparaginase. PEG-asparaginase has been given as an injection in the past and has been used in treatment with both children and adults with ALL. Information from those other research studies suggests that intravenous PEG-asparaginase has been administered safely in both children and adults. We hope to gain more information about the participants disease and how it responds to standard chemotherapy drugs used to treat ALL>


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Doxorubicin
Drug: Cytarabine
Drug: Methotrexate
Drug: Vincristine
Drug: Cyclophosphamide
Drug: Methylprednisone
Drug: Hydrocortisone Sodium Succinate
Drug: Dexamethasone
Drug: 6-MP
Drug: PEG-Asparaginase
Drug: Imatinib
Drug: Etoposide
Procedure: Radiation Therapy
Drug: E. coli Asparaginase
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ALL Adult Consortium Trial: Adult ALL Trial

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To determine the feasibility, toxicity and efficacy of the high-risk pediatric treatment in adult patient 18 year of age or older. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the complete response rate at the end of induction therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival, defined as the time from achieving a complete remission to the first of disease recurrence or death, will be estimated using Kaplan-Meier methods. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall survival, defined as time from study entry to death from any cause, will be estimated using Kaplan-Meier methods. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: April 2007
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Complete remission achieved after Induction Phase
Drug: Doxorubicin
Induction: Intravenously on days 4 and 5. Consolidation 1A: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously day 1 of each cycle.
Drug: Cytarabine
Prophase: Intravenously on days 1-3. Induction: Intrathecal on days 15 or 18. Consolidation IB: Intravenously or subcutaneous on days 2-5 and 9-12. Consolidation IC: Intravenously every 12 hours starting on day 1 CNS Therapy: Intrathecal 4 times over 2 weeks. Consolidation II: Intrathecal once every 18 weeks Continuation: Intrathecal every 18 weeks
Drug: Methotrexate

Induction: Intravenously on day 6 and intrathecally on day 29 or 32. Consolidation IA: Intravenously on day 1 and intrathecally on Day 1 (prior to IV).

Consolidation IB: Intrathecally on day 1. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation: Intrathecally once every 18 weeks. Continuation: Intravenously weekly and intrathecally every 18 weeks.

Drug: Vincristine
Induction: Intravenously on days 4, 11, 18, 25. Consolidation IA: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously on day 1 of each cycle.
Drug: Cyclophosphamide
Consolidation IB: Intravenously on day 1
Drug: Methylprednisone
Prophase: Intravenously on days 1-3
Drug: Hydrocortisone Sodium Succinate
Induction: Intrathecally on day 15 or 18. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation II: Intrathecally once every 18 weeks. Continuation: Intrathecally every 18 weeks.
Drug: Dexamethasone
Consolidation IC: Orally on days 1-5 twice per day. Consolidation II: Orally on days 1-5 of each cycle. Continuation: Orally on days 1-5 of each cycle.
Drug: 6-MP
Induction: Orally on days 3-43 or 33-46. Consolidation IA: orally on days 1-14. Consolidation IB: orally on days 1-14. CNS Therapy: Orally on days 1-14. Consolidation II: Orally on days 1-14. Continuation: Orally on days 1-14 of each cycle.
Drug: PEG-Asparaginase

Consolidation IC: Intravenously every 3 weeks, starting on day 8. CNS Therapy: Intravenously every 3 weeks, starting 3 weeks after the Consolidation IC dose.

Consolidation II: Intravenously every 3 weeks.

Drug: Imatinib
Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.
Drug: Etoposide
Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.
Procedure: Radiation Therapy
Given during CNS Therapy either 8 or 10 daily treatments, on days 1-8 or 1-10, depending upon leukemia involvement in the CSF
Drug: E. coli Asparaginase
Intramuscularly Day 7 of Induction.
Experimental: Arm B
Failure to achieve complete remission after the Induction Phase
Drug: Doxorubicin
Induction: Intravenously on days 4 and 5. Consolidation 1A: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously day 1 of each cycle.
Drug: Cytarabine
Prophase: Intravenously on days 1-3. Induction: Intrathecal on days 15 or 18. Consolidation IB: Intravenously or subcutaneous on days 2-5 and 9-12. Consolidation IC: Intravenously every 12 hours starting on day 1 CNS Therapy: Intrathecal 4 times over 2 weeks. Consolidation II: Intrathecal once every 18 weeks Continuation: Intrathecal every 18 weeks
Drug: Methotrexate

Induction: Intravenously on day 6 and intrathecally on day 29 or 32. Consolidation IA: Intravenously on day 1 and intrathecally on Day 1 (prior to IV).

Consolidation IB: Intrathecally on day 1. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation: Intrathecally once every 18 weeks. Continuation: Intravenously weekly and intrathecally every 18 weeks.

Drug: Vincristine
Induction: Intravenously on days 4, 11, 18, 25. Consolidation IA: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously on day 1 of each cycle.
Drug: Cyclophosphamide
Consolidation IB: Intravenously on day 1
Drug: Methylprednisone
Prophase: Intravenously on days 1-3
Drug: Hydrocortisone Sodium Succinate
Induction: Intrathecally on day 15 or 18. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation II: Intrathecally once every 18 weeks. Continuation: Intrathecally every 18 weeks.
Drug: Dexamethasone
Consolidation IC: Orally on days 1-5 twice per day. Consolidation II: Orally on days 1-5 of each cycle. Continuation: Orally on days 1-5 of each cycle.
Drug: 6-MP
Induction: Orally on days 3-43 or 33-46. Consolidation IA: orally on days 1-14. Consolidation IB: orally on days 1-14. CNS Therapy: Orally on days 1-14. Consolidation II: Orally on days 1-14. Continuation: Orally on days 1-14 of each cycle.
Drug: PEG-Asparaginase

Consolidation IC: Intravenously every 3 weeks, starting on day 8. CNS Therapy: Intravenously every 3 weeks, starting 3 weeks after the Consolidation IC dose.

Consolidation II: Intravenously every 3 weeks.

Drug: Imatinib
Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.
Drug: Etoposide
Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.
Procedure: Radiation Therapy
Given during CNS Therapy either 8 or 10 daily treatments, on days 1-8 or 1-10, depending upon leukemia involvement in the CSF
Drug: E. coli Asparaginase
Intramuscularly Day 7 of Induction.

Detailed Description:
  • This study has several periods of treatment called phases and uses several different drugs in each phase. The drugs may be given by mouth, into a vein, or into the spinal fluid (called intrathecal chemotherapy). In some individuals this treatment helps prevent leukemia cells from coming back in the spinal fluid and brain. Radiation therapy will also be administered as part of this treatment regimen.
  • The treatment program consists of 2-different treatment arms with six separate phases of therapy. The phases of treatment are: (1) Steroid prophase (2) Induction (3) Consolidation I (4) Central nervous system (CNS) therapy (5) Consolidation II (6) Continuation.
  • The participants treatment arm will depend on the status of their leukemia at the end of the induction therapy (the second phase of treatment). Arm A: all participants who achieve complete remission after Induction and Arm B: all participants who fail to achieve a complete remission after Induction.
  • Steroid Prophase: All participants are involved in this treatment phase which consists of two drugs, one given intravenously (IV) and one given intrathecally. This phase lasts 3 days and the purpose is to collect scientific data that might be useful in the future and to see how steroids work in treating leukemia
  • Induction: This phase begins immediately after the steroid prophase and lasts about 1 month. Induction is used to cause a remission. Eight drugs are used during this phase of treatment, and administration is either orally, IV or intrathecal. On day 29, participant's bone marrow and peripheral blood counts will be tested. If they have achieved complete remission or partial remission, they will proceed to the next phase of treatment. If they are not in complete remission, they will receive vincristine by IV on days 32, 39 and 46, until complete remission is achieved. If they do not achieve complete or partial remission by day 53 they will be removed from the study.
  • Consolidation I: This phase of treatment begins as soon as there is a documented confirmation that the participant's leukemia is either in complete or partial remission. Treatment in this phase lasts about 7 weeks and is intended to further reduce the number of leukemia cells in the body. This consolidation treatment consists of 3 phases: 1A, 1B and 1C. Each phase involves a three week cycle of chemotherapy. Arm A and Arm B will be assigned according to remission status after induction therapy and will determine the order that the participant follows the Consolidation phases.
  • Central Nervous System (CNS) Therapy: CNS therapy begins 3 weeks after the end of Consolidation I therapy and should last 3 weeks. Treatment includes a series of lumbar punctures with the administration of anti-leukemia drug as well as oral drugs and IV drugs. Radiation therapy will also be given during this phase of therapy. The purpose of radiation therapy is to prevent leukemia from coming back in the brain. Radiation therapy will be given in either 8 or 10 daily treatments.
  • Consolidation II Therapy: This phase begins as soon as CNS therapy ends and lasts about 27-30 weeks. It consists of cycles of chemotherapy repeated every three weeks along with IV PEG-asparaginase administered every 3 weeks. The cycles will be repeated until the participant receives a total of 10 doses of asparaginase.
  • Continuation Therapy: This phase begins after the end of the Consolidation II phase. The goal of this phase is to get rid of all leukemia in the body. It consists of cycles of chemotherapy repeated every three weeks and will last until the participant has been in remission for two years.
  • During all phases of treatment, participants will have tests and procedures to monitor their health and for research purposes.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8)
  • Age 18.00-50.99 years

Exclusion Criteria:

  • Prior anti-leukemic therapy except 1 week or less of steroids, and/or emergent radiation therapy to the mediastinum, or hydroxyurea or emergent leukopheresis
  • Known HIV positive
  • Secondary ALL
  • Pregnant or breast feeding women
  • Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely
  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: NCT00476190

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Utah
LDS Hospital
Salt Lake City, Utah, United States, 84143
Canada, British Columbia
Vancouver Cancer Center
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
Cancer Care Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
The Moncton Hospital
Moncton, New Brunswick, Canada
Canada, Nova Scotia
QEII, Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Hopital Charles LeMoyne
Greenfield Park, Quebec, Canada, J4V 2H1
McGill University Department of Oncology
Montreal, Quebec, Canada
Hopital Notre-Dame
Montreal, Quebec, Canada
Hopital Maisonneuve Rosemont
Montreal, Quebec, Canada, H1T 2M4
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Children's Hospital Boston
NCIC Clinical Trials Group
Investigators
Principal Investigator: Daniel DeAngelo, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Daniel J. DeAngelo, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00476190     History of Changes
Other Study ID Numbers: 06-254
Study First Received: May 18, 2007
Last Updated: February 11, 2014
Health Authority: United States: Institutional Review Board
Canada: Health Canada

Keywords provided by Dana-Farber Cancer Institute:
ALL

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Methotrexate
Pegaspargase
Dexamethasone
Asparaginase
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 16, 2014