Description:
This phase I trial studies the best dose and side effects of liposomal cytarabine,
daunorubicin, and gemtuzumab ozogamicin in treating pediatric patients with acute myeloid
leukemia that has returned after treatment (relapsed) or does not respond to treatment
(refractory). Chemotherapy drugs, such as liposomal cytarabine and daunorubicin, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Gemtuzumab ozogamicin is a monoclonal
antibody, called gemtuzumab, linked to a toxic agent called ozogamicin. Gemtuzumab attaches
to CD33 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving
liposomal cytarabine and daunorubicin and gemtuzumab ozogamicin may help to control the
disease.
Title
- Brief Title: Liposomal Cytarabine, Daunorubicin, and Gemtuzumab Ozogamicin for the Treatment of Relapsed Refractory Pediatric Patients With Acute Myeloid Leukemia
- Official Title: A Phase I Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Gemtuzumab Ozogamicin (GO) in Relapsed Refractory Pediatric Patients With Acute Myeloid Leukemia (AML)
Clinical Trial IDs
- ORG STUDY ID:
2020-0484
- SECONDARY ID:
NCI-2020-13915
- SECONDARY ID:
2020-0484
- NCT ID:
NCT04915612
Conditions
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
- Recurrent Acute Myeloid Leukemia
- Refractory Acute Myeloid Leukemia
- Secondary Acute Myeloid Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Gemtuzumab Ozogamicin | Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676 | Treatment (CPX-351, GO) |
Liposome-encapsulated Daunorubicin-Cytarabine | CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Daunorubicin and Cytarabine (Liposomal), Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos | Treatment (CPX-351, GO) |
Purpose
This phase I trial studies the best dose and side effects of liposomal cytarabine,
daunorubicin, and gemtuzumab ozogamicin in treating pediatric patients with acute myeloid
leukemia that has returned after treatment (relapsed) or does not respond to treatment
(refractory). Chemotherapy drugs, such as liposomal cytarabine and daunorubicin, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Gemtuzumab ozogamicin is a monoclonal
antibody, called gemtuzumab, linked to a toxic agent called ozogamicin. Gemtuzumab attaches
to CD33 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving
liposomal cytarabine and daunorubicin and gemtuzumab ozogamicin may help to control the
disease.
Detailed Description
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) and safety of liposomal cytarabine and
daunorubicin (CPX-351) in combination with gemtuzumab ozogamicin (GO) in relapsed refractory
pediatric patients with acute myeloid leukemia (AML).
SECONDARY OBJECTIVE:
I. To determine the preliminary assessment of efficacy by overall response (OR), including
complete remission (CR), CR with incomplete blood count recovery and partial remission),
overall survival (OS), event-free survival (EFS) and duration of response (DOR) of pediatric
patients treated with this combination.
EXPLORATORY OBJECTIVES:
I. To determine the minimal residual disease (MRD) after treatment with this combination and
its impact in long-term outcome (OS and EFS).
II. To determine the effect of the level of pre-treatment expression of CD33 with response to
this combination.
III. To determine the effect of this treatment combination on responding pediatric patients
transitioning to hematopoietic stem cell transplant (HSCT) i.e., number and percentage of
patients that are able to transition to HSCT.
OUTLINE:
INDUCTION 1 (28 days): Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1,
3, and 5 and GO IV over 2 hours on day 1 in the absence of disease progression or
unacceptable toxicity.
INDUCTION 2: Patients who do not attain a defined clinical response after cycle Induction 1
receive CPX-351 IV on days 1 and 3 and GO IV over 2 hours on day 1 in the absence of disease
progression or unacceptable toxicity.
CONSOLIDATION: Beginning 4 weeks after last induction, patients receive CPX-351 IV over 90
minutes on days 1 and 3 and GO IV over 2 hours on day 1 in the absence of disease progression
or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (CPX-351, GO) | Experimental | INDUCTION 1 (28 days): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and GO IV over 2 hours on day 1 in the absence of disease progression or unacceptable toxicity.
INDUCTION 2: Patients who do not attain a defined clinical response after cycle Induction 1 receive CPX-351 IV on days 1 and 3 and GO IV over 2 hours on day 1 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Beginning 4 weeks after last induction, patients receive CPX-351 IV over 90 minutes on days 1 and 3 and GO IV over 2 hours on day 1 in the absence of disease progression or unacceptable toxicity. | - Gemtuzumab Ozogamicin
- Liposome-encapsulated Daunorubicin-Cytarabine
|
Eligibility Criteria
Inclusion Criteria:
- Pediatric patients with diagnosis of CD33 positive (> 3%),
- Newly diagnosed secondary AML
- Relapsed refractory acute myeloid leukemia by World Health Organization (WHO)
criteria Patients must have >= 5% blasts in the bone marrow as assessed by
morphology or flow cytometry. However, if an adequate bone marrow sample cannot
be obtained, patients may be enrolled if there is unequivocal evidence of
leukemia with >= 5% blasts in the peripheral blood
- Pediatric Patients with myelodysplastic syndrome (MDS) who progress to AML are
eligible at the time of diagnosis of AML regardless of any prior therapy for MDS
- Performance status: Lansky >= 50 for patients who are =< 16 years old and Karnofsky >=
50% for patients who are > 16 years old
- Age =< 21 years of age
- Total serum bilirubin =< 2 x upper limit of normal (ULN). Patients with known
Gilbert's syndrome may have a total bilirubin up to =< 3 x ULN
- Serum creatinine =< 2.0 mg/dl
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x ULN; =<
5 x ULN in case of suspected leukemic liver involvement
- Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotropin (beta-HCG) pregnancy test result within 14 days prior to the
first dose of study drugs and must agree to use one of the following effective
contraception methods during the study and for 30 days following the last dose of
study drug. Effective methods of birth control include:
- Birth control pills, skin patches, shots, implants (placed under the skin by a
health care provider)
- Intrauterine devices (IUDs)
- Condom or occlusive cap (diaphragm or cervical/vault caps) used with Spermicide
- Abstinence
- Males, need to inform the doctor right away if the partner becomes pregnant or
suspects pregnancy. While in this study and for 30 days after the last treatment the
patient should not donate sperm for the purposes of reproduction. He will need to use
a condom while in this study and for 30 days after the last treatment
Exclusion Criteria:
- History of another primary invasive malignancy that has not been definitively treated
and in remission. Patients with non-melanoma skin cancers or with carcinomas in situ
are eligible regardless of the time from diagnosis (including concomitant diagnoses)
- Presence of clinically significant uncontrolled central nervous system (CNS) pathology
such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries,
organic brain syndrome, or psychosis
- Evidence of active cerebral/meningeal disease. Patients may have history of CNS
leukemic involvement if definitively treated with prior therapy and no evidence of
active disease at the time of consent with at least 2 consecutive spinal fluid
negative assessments for residual leukemia and negative imaging (imaging required only
if previously showing evidence of CNS leukemia not otherwise documented by spinal
fluid assessment)
- Patients with a cardiac ejection fraction (as measured by either multigated
acquisition scan [MUGA] or echocardiogram) < 50% are excluded
- Patients with total cumulative doses of non-liposomal daunorubicin, or other
anthracycline equivalent, greater than 450 mg/m^2
- Patients with uncontrolled, active infections (viral, bacterial, or fungal).
Infections controlled on concurrent anti-microbial agents are acceptable, and
anti-microbial prophylaxis per institutional guidelines are acceptable
- Known active hepatitis B or C infection, or known seropositivity for human
immunodeficiency virus (HIV)
- Liver cirrhosis or other serious active liver disease or with suspected active alcohol
abuse
- Active acute/chronic graft-versus-host disease (GvHD) requiring systemic treatment; or
receiving immunosuppression for GvHD prophylaxis within 2 weeks from the start of
study therapy
- Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the
start of study drugs with the following exception:
- To reduce the circulating blast count or palliation: Single dose intravenous
cytarabine or hydroxyurea. No washout necessary for these agents
- Females who are pregnant or lactating
- Male or female subjects of childbearing potential, unwilling to use an approved,
effective means of contraception in accordance with institution's standards
- Other severe, uncontrolled acute or chronic medical or psychiatric condition or
laboratory abnormality that in the opinion of the Investigator may increase the risk
associated with study participation or investigational product administration or may
interfere with the interpretation of study results and/or would make the patient
inappropriate for enrollment into this study
- Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic
leukemia, or bone marrow failure syndromes are not eligible
Maximum Eligible Age: | 21 Years |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose |
Time Frame: | Up to 28 days |
Safety Issue: | |
Description: | Will employ the Bayesian optimal interval (BOIN) design. |
Secondary Outcome Measures
Measure: | Objective response |
Time Frame: | Up to 28 days |
Safety Issue: | |
Description: | Will be summarized using descriptive statistics overall and per dose levels. |
Measure: | Duration of response |
Time Frame: | Number of days from the date of initial response (partial response or better) to the date of first documented disease progression/relapse or death, whichever occurs first, assessed p to 28 days |
Safety Issue: | |
Description: | Will be summarized using descriptive statistics overall and per dose levels. |
Measure: | Overall survival |
Time Frame: | Number of days from study enrollment to death due to any cause, assessed up to 28 days |
Safety Issue: | |
Description: | Will be estimated using Kaplan-Meier method. |
Measure: | Event free survival |
Time Frame: | Number of days from the date of treatment initiation to the date of documented treatment failure, relapses from complete response, or death from any cause, whichever occurs first, assessed up to 28 days |
Safety Issue: | |
Description: | Will be estimated using Kaplan-Meier method. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
June 7, 2021