Acute Lymphoblastic Leukemia, Lymphoid Leukemia, Refractory Acute Lymphoblastic Leukemia, Relapsed Acute Lymphoblastic Leukemia
Conditions
Keywords
T-cell acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia
Brief summary
This study involves Vyxeos (CPX-351), a formulation of a fixed combination of the two anti-tumor drugs, cytarabine and daunorubicin that will be given as an infusion over 90 minutes. This study will use what is called a liposome injection. This is a special fat capsule (called a liposome) that surrounds the cytarabine and daunorubicin and protects the drugs from being eliminated/destroyed by the body.
Interventions
DRUGCPX-351
The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period.
Sponsors
Jazz Pharmaceuticals
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open label, single arm, single center, phase 2 pilot study of Vyxeos induction & consolidation in relapsed and refractory ALL.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent/assent for the trial. * Be ≥ 18 years of age on day of signing informed consent. * Able to adhere to the study visit schedule and other protocol requirements. * Pathologically confirmed B- or T-cell acute lymphoblastic or mixed phenotype acute leukemia, with \>5% peripheral blood or bone marrow lymphoblasts and/or extramedullary disease \>1x1cm. * Relapsed or refractory acute lymphoblastic leukemia after at least 1 prior cycle of therapy. Patients with Philadelphia chromosome positive disease must have failed at least two prior tyrosine kinase inhibitors. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Cardiac ejection fraction ≥ 50% by echocardiography or multigated acquisition scan (MUGA). * Must be at least 2 weeks out from any prior systemic chemotherapy, blinatumumab, radiation, and/or other investigational agents, and have recovered to grade 1 from any toxicity related to prior therapy. Glucocorticoids are permitted up to 1 day prior to the first dose. * Serum bilirubin and creatinine less than 1.5x upper limit of normal (ULN). AST and ALT must be less than 3x ULN, unless there is suspected liver involvement. * 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 contraception, be surgically sterile, or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study treatment. * Male participants 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
Exclusion criteria
* Clinical evidence of active central nervous system (CNS) leukemia. * Any major surgery or radiation therapy within four weeks. * 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 severe graft-versus-host disease, unstable angina, pulmonary hypertension, active/prior veno-occlusive disease of the liver or severe CHF (NYHA III-IV). * Patients with active (uncontrolled, metastatic) second malignancies. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 after the last dose of trial treatment. * Hypersensitivity to cytarabine, daunorubicin, or liposomal products. * History of Wilson's disease or other copper-metabolism disorder. * Patients with prior cumulative anthracycline exposure of greater than 368 mg/m\^2 daunorubicin or equivalent).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate (CR) + CR With Incomplete Recovery (CRi) | At day 28 | Expansion from phase II pilot to a phase II trial will depend on demonstration of CR/CRi amongst 4 of the initial 10 treated patients. Investigators will measure remission rate at day 28 to address the primary endpoint of complete remission (with or without complete hematologic recovery), as defined by Cheson Criteria (ref 27). For those with extramedullary disease, Lugano criteria will be used to assess response. This is a standard assessment of drug efficacy for phase 2 clinical trial design in acute leukemias, as response correlates closely with progression free- and overall survival (PFS and OS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 12 months | Progression Free Survival as defined by Cheson and Lugano Criteria, namely progression, failure to respond, or death, as assessed from time of first treatment. Progression Free Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment. |
| Overall Survival (OS) | 12 months | Overall Survival as defined by Cheson and Lygano Criteria, namely death due to any cause as assessed from time of first treatment. Overall Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment. |
| Minimal Residual Disease (MRD) | At day 28 | MRD assessment will be provided using ClonoSeq test result. ClonoSEQ® is an FDA-cleared test used to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CPX-351 Treatment Participants will receive induction with CPX-351 at a dose of 100 u/m\^2 administered intravenously over 90 minutes on days 1, 3 and 5 of a 28 day cycle.
This may be followed by consolidation with CPX-351 at a dose of 65 u/m\^2 administered intravenously over 90 minutes on days 1 and 3 of a 28 day cycle (up to 3 cycles).
CPX-351: The infusion of CPX-351 (cytarabine:daunorubicin) Liposome Injection will be performed through a central venous catheter, using an infusion pump to ensure that the drug is infused over the specified time period. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | CPX-351 Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 7 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 7 / 7 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 2 / 7 | 1 / 3 | 1 / 1 |
Outcome results
Primary
Complete Remission Rate (CR) + CR With Incomplete Recovery (CRi)
Expansion from phase II pilot to a phase II trial will depend on demonstration of CR/CRi amongst 4 of the initial 10 treated patients. Investigators will measure remission rate at day 28 to address the primary endpoint of complete remission (with or without complete hematologic recovery), as defined by Cheson Criteria (ref 27). For those with extramedullary disease, Lugano criteria will be used to assess response. This is a standard assessment of drug efficacy for phase 2 clinical trial design in acute leukemias, as response correlates closely with progression free- and overall survival (PFS and OS).
Time frame: At day 28
Population: Evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CPX-351 Treatment | Complete Remission Rate (CR) + CR With Incomplete Recovery (CRi) | 30 Percent of participants |
Secondary
Minimal Residual Disease (MRD)
MRD assessment will be provided using ClonoSeq test result. ClonoSEQ® is an FDA-cleared test used to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL).
Time frame: At day 28
Population: Evaluable participants - Participants who achieved CR or CRi
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CPX-351 Treatment | Minimal Residual Disease (MRD) | Complete Molecular Remission by ClonoSeq | 1 Participants |
| CPX-351 Treatment | Minimal Residual Disease (MRD) | No trackable clone by ClonoSeq | 2 Participants |
Secondary
Overall Survival (OS)
Overall Survival as defined by Cheson and Lygano Criteria, namely death due to any cause as assessed from time of first treatment. Overall Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment.
Time frame: 12 months
Population: Evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CPX-351 Treatment | Overall Survival (OS) | 218 Days |
Secondary
Progression Free Survival (PFS)
Progression Free Survival as defined by Cheson and Lugano Criteria, namely progression, failure to respond, or death, as assessed from time of first treatment. Progression Free Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment.
Time frame: 12 months
Population: Evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CPX-351 Treatment | Progression Free Survival (PFS) | 57 Days |