ALL Adult Consortium Trial: Adult ALL Trial - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute Massachusetts General Hospital Children's Hospital Boston
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00476190

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 a drug called PEG-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	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Cytarabine Cytarabine hydrochloride Etoposide Mercaptopurine 6-Mercaptopurine L-Asparaginase Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Hydrocortisone Cortisol 21-phosphate Cortisol succinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone acetate Hydrocortisone cypionate Hydrocortisone hemisuccinate Proctofoam-HC Methotrexate Vincristine sulfate Vincristine Imatinib Imatinib mesylate Succinic acid Etoposide phosphate Pegaspargase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Parallel Assignment, Efficacy Study
Official Title:	ALL Adult Consortium Trial: Adult ALL Trial

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:	60
Study Start Date:	April 2007
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Experimental 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 (proior 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: Intrathecallly 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 Induction: Intravenously on day 7. Consolidation IC: Intravenously every 2 weeks, starting on day 8. CNS Therapy: Intravenously every 2 weeks, starting on day 1. Consolidation II: Intravenously every 2 weeks, starting on day 1 of each cycle. Drug: Imatinib Used for PH+ ALL subjects 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
Arm B: Experimental 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 (proior 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: Intrathecallly 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 Induction: Intravenously on day 7. Consolidation IC: Intravenously every 2 weeks, starting on day 8. CNS Therapy: Intravenously every 2 weeks, starting on day 1. Consolidation II: Intravenously every 2 weeks, starting on day 1 of each cycle. Drug: Imatinib Used for PH+ ALL subjects 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

Arms

Assigned Interventions

Arm A: Experimental

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 (proior 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: Intrathecallly 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

Induction: Intravenously on day 7. Consolidation IC: Intravenously every 2 weeks, starting on day 8. CNS Therapy: Intravenously every 2 weeks, starting on day 1. Consolidation II: Intravenously every 2 weeks, starting on day 1 of each cycle.

Drug: Imatinib

Used for PH+ ALL subjects 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

Arm B: Experimental

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 (proior 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: Intrathecallly 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

Induction: Intravenously on day 7. Consolidation IC: Intravenously every 2 weeks, starting on day 8. CNS Therapy: Intravenously every 2 weeks, starting on day 1. Consolidation II: Intravenously every 2 weeks, starting on day 1 of each cycle.

Drug: Imatinib

Used for PH+ ALL subjects 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

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 2 weeks. The cycles will be repeated until the participant receives a total of 15 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00476190

Contacts

Contact: Daniel DeAngelo, MD

617-632-2645

ddeangelo@partners.org

Locations

United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Daniel DeAngelo, MD
Massachusetts General Hosptiatl	Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Philip Amrein, MD
Children's Hospital of Boston	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Lewis Silverman, MD

Sponsors and Collaborators

Dana-Farber Cancer Institute

Massachusetts General Hospital

Children's Hospital Boston

Investigators

Principal Investigator:

Daniel DeAngelo, MD

Dana-Farber Cancer Institute

More Information

Responsible Party:	Dana-Farber Cancer Institute ( Daniel DeAngelo, MD, PhD )
Study ID Numbers:	06-254
Study First Received:	May 18, 2007
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00476190
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

ALL

Study placed in the following topic categories:

Dexamethasone
Leukemia, Lymphoid
Hydrocortisone
Cyclophosphamide
6-Mercaptopurine
Etoposide phosphate
Acute lymphoblastic leukemia, adult
Leukemia
Pegaspargase
Methotrexate
Lymphoma
Etoposide
Dexamethasone acetate

Cytarabine
Asparaginase
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cortisol succinate
Vincristine
Doxorubicin
Imatinib
Folic Acid
Lymphatic Diseases
Hydrocortisone acetate
Lymphoproliferative Disorders

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Reproductive Control Agents
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Abortifacient Agents

Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Mitosis Modulators
Gastrointestinal Agents
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Antiviral Agents
Glucocorticoids

ClinicalTrials.gov processed this record on January 16, 2009