CalPeg for Newly Diagnosed Acute Lymphoblastic Leukemia (... | NCT05581030

NCT05581030

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Servier	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Hyper-CVAD + Calaspargase pegol Treatment	Experimental	Participants will receive calaspargase pegol administered over 1 hour with each cycle of Hyper-CVAD, mini-CVD, and late intensification, beginning with Cycle 1B. Responding patients will have dose reduction of HyperCVAD for Cycles 2B-4B. Participants with CD20+ ALL will also be given Rituximab once per cycle.	Drug: Hyper CVAD Protocol (Standard of Care Multi-Agent Chemotherapy) Drug: Calaspargase Pegol Drug: Rituximab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Hyper CVAD Protocol (Standard of Care Multi-Agent Chemotherapy)	Drug	Hyper-CVAD consists of two combinations of drugs (courses A and B) given in an alternating fashion. The term "hyper" refers to the hyperfractionated nature of the chemotherapy, which is given in small doses, more frequently, to minimize side effects. CVAD is the acronym of the drugs in course a: cyclophosphamide, vincristine, doxorubicin and dexamethasone. Course A: Cyclophosphamide days 1, 2 and 3. Vincristine days 4 and 11, Doxorubicin day 4, dexamethasone days 1-4 and 11-14, Cytarabine day 7. Mesna is also given orally with cyclophosphamide, to reduce the incidence of haemorrhagic cystitis, a common side effect of cyclophosphamide. Methotrexate, an antimetabolite, may be given when necessary to get chemotherapy past the blood brain barrier. Course B: Methotrexate Day 1 and Cytarabine Days 2 and 3. Dosage is individualized to the patient.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mortality Rate of Hyper-CVAD after first infusion of calaspargase pegol	Mortality rate is hypothesized to be less than 10% when combining calaspargase pegol with Hyper-CVAD.	Up to 12 months

Secondary Outcomes

Measure	Description	Time Frame
Minimal Residual Disease Remission Rate	Minimal Residual Disease (MRD) will be studied as a dichotomous endpoint using a cutoff of 1x10^4 cells/transcripts as the lower limit for residual leukemia and presented as the percentage of patients reaching this landmark as their best response. MRD assessment will be obtained with each bone marrow biopsy assessment, every 3 months in the first year following their last cycle of therapy and every 6 months in the subsequent 2 years following their last cycle.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologically confirmed Philadelphia negative B- or T-cell acute lymphoblastic leukemia, with >10% peripheral blood or bone marrow lymphoblasts at diagnosis.
Treatment and full recovery from arm 1A of the Hyper-CVAD regimen.
Be willing and able to provide written informed consent/assent for the trial.
Able to adhere to the study visit schedule and other protocol requirements.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Cardiac ejection fraction ≥ 50% by echocardiography or MUGA, as measured prior to arm 1A of Hyper-CVAD.
Serum bilirubin and creatinine < 1.5x upper limit of normal (ULN). AST and ALT must be <3x ULN.
Females of childbearing potential (FCBP) must have a negative serum pregnancy test at screening. A FCBP is considered when a sexually mature female: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months.
A FCBP must agree to use of two methods of highly effective non-hormonal contraception, be surgically sterile, or abstain from heterosexual activity for the course of the study through 3 monthsafter the last dose of study treatment.
Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 30 days after the last dose of study therapy. Men must agree to not donate sperm during and after the study for 3 months

Exclusion Criteria:

Induction therapy with any regimen other than Hyper-CVAD 1A.
Diagnosis of L3 type Burkitt's lymphoma
Clinical evidence of active central nervous system (CNS) leukemia.
Any major surgery or radiation therapy within four weeks.
Diagnosis of Down Syndrome.
Any active infection requiring systemic therapy, including HIV, Hepatitis B, and/or Hepatitis C.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator (including but not limited to unstable angina, pre-existing liver disease, recurrent pancreatitis, uncontrolled diabetes, hypertriglyceridemia, pulmonary hypertension, or severeheart failure (New York Heart Association Class III-IV).
Recurrent thrombosis, or non-central venous catheter associated thrombosis within 3 months prior to enrollment.
Severe comorbid conditions for which life expectancy would be <6 months.
Patients with active (uncontrolled, metastatic) second malignancies are excluded.
Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 3 months after the last dose of trial treatment.

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins