Acute Lymphoblastic Leukemia, B-cell Adult Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, T-cell Adult Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute lymphoblastic Leukemia, Lymphoblastic lymphoma, B-cell Adult Acute Lymphoblastic Leukemia, T-cell Adult Acute Lymphoblastic Leukemia
Brief summary
This research study is evaluating a combination of drugs considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new drug called MLN 9708. Additionally, the study is also evaluating if bone marrow or stem cell transplantation, which will be given to some participants, helps to prevent ALL from returning.
Detailed description
In this research study, the investigators are studying the optimal dose of the drug MLN 9708 when given with a standard multi-drug regimen. In the first part of the study, up to 18 participants will be enrolled at different doses of MLN 9708. Once the maximally tolerated (highest, safest dose) is established, an additional 10 participants will be enrolled. Additionally, bone marrow (tissue found in the inside of bones) or stem cell transplantation will be given to some participants to study whether it helps to prevent ALL from returning. The study treatment consists of several different stages * Induction * Consolidation 1 * Or Stem Cell or Bone Marrow Transplant (if you are eligible based on your medical condition and the availability of a matched stem cell donor) * Or If you do not have a transplant: * CNS Therapy * Consolidation 2 * Continuation Therapy
Interventions
DRUGMLN 9708
Patients will received standard chemotherapy as well as MLN 9708 in escalating doses.
DRUGVincristine
Standard chemotherapy dosage and duration
DRUGCytarabine
Standard chemotherapy dosage and duration
DRUGDoxorubicin
Standard chemotherapy dosage and duration
DRUGMercaptopurine
Standard chemotherapy dosage and duration
DRUGCyclophosphamide
Standard chemotherapy dosage and duration
DRUGMethotrexate
Standard chemotherapy dosage and duration
Sponsors
Millennium Pharmaceuticals, Inc.
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
51 Years to 75 Years
Healthy volunteers
No
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). * Patients with mature B-cell ALL will be removed from the protocol as soon as that diagnosis is made and should be treated on a B-cell leukemia (Burkitt's) protocol. NOTE: Patients with T-cell surface markers and a t(8;14)(q24;q11) remain eligible. * Patients with lymphoblastic lymphoma are also eligible * No prior anti-leukemic therapy except the following are allowed: \<1 week of corticosteroids, or hydroxyurea or emergent leukopheresis. Longer steroid use for diseases other than leukemia is permitted. * Age 51- 75 years * Voluntary written consent must be given before performance of any study-related procedures not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. * If patient is known to be HIV positive, they will not be eligible for the protocol. HIV testing is not mandatory prior to protocol enrollment. * Patients whose comorbid medical condition, in the investigator's opinion, would make participation in this trial and adherence to the protocol guidelines difficult should be excluded. * Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely are excluded. * Ejection fraction ≥ 45% * Creatinine\<2.0 times upper limit of normal * Total bilirubin \< 1.5 times upper limit of normal except for known conjugation diseases such as Gilbert's, ALT and AST \<3.0 times upper limit of normal. Direct bilirubin is not an inclusion criteria. * ECOG performance status of 0, 1, 2 * Non pregnant and non lactating Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) * Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
Exclusion criteria
* Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Dose Tolerated of MLN 9708 | 2 Years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patient with Complete Remission (CR) rate at the end of induction therapy | 30 Days | — |
| Percentage of Participants with Disease Free Survival | 2 Years | — |
| Rate of Overall survival (OS) | 1 Year, 2 Year, 3 Year | — |
| Complete Remission Rate | 2 Years | — |
| Rate of Toxicity | 2 Years | Assess adverse events, serious adverse events, neurotoxicity grading |
Countries
United States
Outcome results
None listed