Summary
The goal of this research study is to evaluate a chemotherapy regiment for the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs).
The names of the study drugs involved in this study are:
* blinatumomab (a type of immunotherapy drug)
* cyclophosphamide (a type of chemotherapy drug)
* cytarabine (a type of antineoplastic agent)
* dexamethasone (a type of synthetic glucocorticoid)
* doxorubicin (a type of antineoplastic agent)
* etoposide (a type of antineoplastic agent)
* mercaptopurine (a type of antineoplastic agent)
* methotrexate (a type of chemotherapy drug)
* pegaspargase (a type of antineoplastic agent)
* vincristine (a type of antineoplastic agent)
Detailed Description
This Phase 2, single-arm research study is to evaluate a chemotherapy regiment the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs).
The U.S. Food and Drug Administration (FDA) has approved all of the drugs of treatment being studied but the investigators of this research study want to understand more about the safety and effectiveness of the chemotherapy regimen in adolescents and young adults with newly diagnosed Philadelphia chromosome-negative ALL.
The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, saliva tests, X-rays, electrocardiograms (ECGs), echocardiograms (ECHOs), Dual-Energy X-ray Absorptiometry (DEXA) scans, bone marrow aspirations/biopsies.
Participation in this study is expected to last about 10 years, 2 years of treatment followed by 8 years of follow up.
It is expected that about 67 people will take part in this research study.
Eligibility Criteria
Age Range: 18 years to 51 years
Inclusion Criteria:
3.1.1Confirmed diagnosis of Philadelphia chromosome-negative acute lymphoblastic leukemia.
* Diagnosis should be made by peripheral blood, bone marrow aspirate, bone marrow biopsy, or tissue biopsy demonstrating ≥25% involvement by lymphoblasts, with flow cytometry or immunohistochemistry confirming B-ALL or T-ALL.
o Participants with B-cell and T-cell lymphoblastic lymphoma are eligible regardless of bone marrow involvement Participants with mixed phenotype acute leukemia (MPAL) ARE eligible, if an ALL regimen is felt to be most appropriate treatment.
* Participants with CNS leukemia ARE eligible. 3.1.2 Allowed prior therapy:
* Corticosteroids, hydroxyurea, all-trans retinoic acid (ATRA).
* IT chemotherapy.
* Emergent radiation therapy or leukapheresis for life threatening complications.
* One cycle of prior chemotherapy (i.e. an induction cycle given at another institution and participant transfers care for post-induction treatment; OR a participant does not meet eligibility prior to induction but does meet eligibility after remission induction).
3.1.3 Age 18.00 - 50.99 years 3.1.4 Direct bilirubin \<1.4 mg/dL (total bilirubin \< 1.4 mg/dL is acceptable). 3.1.5 Willingness to use effective means of birth control. The effects of chemotherapy on the developing human fetus are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study.
3.1.6 Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Philadelphia chromosome-positive / BCR::ABL1 fusion 3.2.2 Participants with mature B-cell (Burkitt's) ALL. Mature B-cell ALL is defined by the presence of surface immunoglobulin AND any of the following: t(8;14)(q24;q32), t(8;22), t(2;8), or c-myc-gene rearrangement by FISH, PCR or other testing. \[FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for participants with surface immunoglobulin expression or L3 morphology\]. 3.2.3 Participants with acute undifferentiated leukemia. 3.2.4 Participants receiving any other investigational agent for this condition.
3.2.5 Uncontrolled intercurrent illness including but not limited to ongoing infection with vital sign instability (hypotension, respiratory insufficiency), life-threatening acute tumor lysis syndrome (e.g., with renal failure), symptomatic congestive heart failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding. Circumstances that may significantly interfere with a participant's ability to safely comply with study procedures, such as attend scheduled study visits, adhere to treatment protocols, or complete study assessments. These include a lack of reliable transportation, unstable housing, or psychiatric illness, but reasonable attempts should be made to overcome these circumstances, including but not limited to identifying sponsor, institutional, or thirdparty financial or social support as well as psychiatric consultation for objective assessment. 3.2.6 Sexually active participants of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation are ineligible.
3.2.7 Pregnant women are excluded from this study because many of the agents used on this protocol have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these chemotherapy agents, breastfeeding should be discontinued if the mother is enrolled.