ALL Adult Consortium Trial: Adult ALL Trial

Condition(s) targeted: Acute Lymphoblastic Leukemia

Intervention: 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 (Drug); Radiation Therapy (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Daniel DeAngelo, MD, Principal Investigator, Affiliation: Dana-Farber Cancer Institute

Overall contact:
Daniel DeAngelo, MD, Phone: 617-632-2645, Email: ddeangelo@partners.org

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>

Official title: ALL Adult Consortium Trial: Adult ALL Trial

Study design: Treatment, Non-Randomized, Open Label, Historical Control, Parallel Assignment, Efficacy Study

Primary outcome: To determine the feasibility, toxicity and efficacy of the high-risk pediatric treatment in adult patient 18 year of age or older.

Secondary outcome:

To determine the complete response rate at the end of induction therapy.

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.

Overall survival, defined as time from study entry to death from any cause, will be estimated using Kaplan-Meier methods.

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.

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

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

Daniel DeAngelo, MD, Phone: 617-632-2645, Email: ddeangelo@partners.org

Vancouver Cancer Center, Vancouver, British Columbia V5Z 4E6, Canada; Recruiting
Anna Koochin, RN, Phone: 60 875-4111, Ext: 67409, Email: akoochin@bccancer.bc.ca
Yasser Mourad, MD, Principal Investigator

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Daniel DeAngelo, MD, Principal Investigator

Children's Hospital of Boston, Boston, Massachusetts 02115, United States; Recruiting
Lewis Silverman, MD, Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Christine: Connolly, Phone: 617-726-5131, Email: Cconnolly1@partners.org
Linda Rivera, Phone: 617.724.5253, Email: Lrivera3@partners.org
Karen K Ballen, MD, Principal Investigator

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Celeste Rojas, Phone: 212-342-3590, Email: cr2393@columbia.edu

Ohio State University Medical Center, Columbus, Ohio 43210, United States; Recruiting
Shawna Oxier, Phone: 617-366-8309, Email: Shawna.oxier@osumc.edu
William Blum, MD, Principal Investigator

Cancer Care Manitoba, Winnipeg, Ontario R3E 0V9, Canada; Recruiting
Sandra Yap, Phone: 204-787-2635, Email: Sandra.yap@cancercare.mb.ca
Matthew D Seftel, MD, Principal Investigator

Hopsital Maisonneuve Rosemont, Montreal, Quebec H1T 2M4, Canada; Recruiting
Dominique Beaupre, Email: dbeaupre.hmr@ssss.gouv.qc.ca
Julie Bergeron, MD, Principal Investigator

Hospital Charles LeMoyne, Greenfield Park, Quebec J4V 2H1, Canada; Recruiting
Pierre Desjardins, MD, Email: pierre.desjardins@rrsss16.gouv.qc.ca
Pierre Desjardins, MD, Principal Investigator

LDS Hospital, Salt Lake City, Utah 84143, United States; Recruiting
Suzanne Kaempfer, Phone: 801-408-1819
Julie Asch, MD, Principal Investigator

Starting date: April 2007
Ending date: April 2010
Last updated: June 2, 2009