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

Sponsor:	Dana-Farber Cancer Institute
Collaborators:	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 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 II

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:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia

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

U.S. FDA Resources

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.

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

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, 02215
Contact: Kristina Hines 617-632-6288 khines1@partners.org
Principal Investigator: Daniel DeAngelo, MD
Children's Hospital of Boston	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jessica Allen jallen16@partners.org
Principal Investigator: Lewis Silverman, MD
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Christine: Connolly 617-726-5131 Cconnolly1@partners.org
Principal Investigator: Karen K Ballen, MD
Beth Isreal Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Qiu 617-667-9923 dqiu@bidmc.harvard.edu
Principal Investigator: David Avigan, MD
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Active, not recruiting
New York, New York, United States, 10032
United States, Ohio
Ohio State University Medical Center	Active, not recruiting
Columbus, Ohio, United States, 43210
United States, Utah
LDS Hospital	Active, not recruiting
Salt Lake City, Utah, United States, 84143
Canada, British Columbia
Vancouver Cancer Center	Active, not recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, New Brunswick
The Moncton Hospital	Active, not recruiting
Moncton, New Brunswick, Canada
Canada, Nova Scotia
QEII, Health Sciences Centre	Active, not recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Cancer Care Manitoba	Active, not recruiting
Winnipeg, Ontario, Canada, R3E 0V9
Canada, Quebec
Hopital Charles LeMoyne	Active, not recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
McGill University Department of Oncology	Active, not recruiting
Montreal, Quebec, Canada
Hopital Notre-Dame	Active, not recruiting
Montreal, Quebec, Canada
Hopital Maisonneuve Rosemont	Active, not recruiting
Montreal, Quebec, Canada, H1T 2M4

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

No publications provided

Responsible Party:	Daniel DeAngelo, MD, PhD, 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:	August 4, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

ALL

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
Pegaspargase
Imatinib
Asparaginase
Cyclophosphamide
Cytarabine
Dexamethasone

Doxorubicin
Etoposide
Methotrexate
Vincristine
Dexamethasone acetate
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012