ALL Adult Consortium Trial: Adult ALL Trial

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00476190

Collaborator

Massachusetts General Hospital (Other), Boston Children's Hospital (Other), NCIC Clinical Trials Group (Other)

112

Enrollment

Locations

Arms

188

Duration (Months)

7.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ALL Adult Consortium Trial: Adult ALL Trial

Study Start Date :

Apr 1, 2007

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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

Drug: Methotrexate

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

Drug: PEG-Asparaginase

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.

Outcome Measures

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. [3 years]

Secondary Outcome Measures

To determine the complete response rate at the end of induction therapy. [2 years]
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. [3 years]
Overall survival, defined as time from study entry to death from any cause, will be estimated using Kaplan-Meier methods. [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Children's Hospital of Boston	Boston	Massachusetts	United States	02115
3	Beth Isreal Deaconess Medical Center	Boston	Massachusetts	United States	02215
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
6	Ohio State University Medical Center	Columbus	Ohio	United States	43210
7	LDS Hospital	Salt Lake City	Utah	United States	84143
8	Vancouver Cancer Center	Vancouver	British Columbia	Canada	V5Z 4E6
9	Cancer Care Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
10	The Moncton Hospital	Moncton	New Brunswick	Canada
11	QEII, Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
12	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
13	Hopital Maisonneuve Rosemont	Montreal	Quebec	Canada	H1T 2M4
14	Hopital Notre-Dame	Montreal	Quebec	Canada
15	McGill University Department of Oncology	Montreal	Quebec	Canada