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Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome

Primary Purpose

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, High Risk Myelodysplastic Syndrome

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemtuzumab Ozogamicin
Liposome-encapsulated Daunorubicin-Cytarabine
Quality-of-Life Assessment
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of CD33 positive (>= 3%), relapsed refractory acute myeloid leukemia by World Health Organization (WHO) criteria. Patients with post-hypomethylating agent (post-HMA) failure high-risk myelodysplastic syndrome (MDS), as defined by the presence of > 10% blasts, are also eligible.
  • Patients with MDS or chronic myelomonocytic leukemia (CMML) who received hypomethylating agent based-therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless of any prior therapy for MDS or CMML. The WHO classification will be used for AML.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2.
  • 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 (b-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, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; abstinence.
  • Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy.
  • Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug.
  • Patients or their legally authorized representative must provide written informed consent.

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 or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, 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 active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV. 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 200 mg/m^2.
  • Patients with uncontrolled, active infections (viral, bacterial, or fungal).
  • Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV).
  • Patients with liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse.
  • Allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months before the start of protocol-specified therapy, or with 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.
  • Patients must have recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment.
  • 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.
  • Prior treatment with CPX-351 or gemtuzumab ozogamicin.

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (CPX-351, gemtuzumab ozogamicin)

Arm Description

INDUCTION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 of cycle 1 and days 1 and 3 of cycle 2 and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity. CONSOLIDATION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity. MAINTENANCE CYCLE: Patients receive gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall response rate
Will use the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia and Myelodysplasia. Will estimate the ORR for the combination treatment, along with the 95% credible interval.
Incidence and severity of all adverse events assessed using Common Toxicity Criteria version 4.0

Secondary Outcome Measures

Demographic/clinical characteristics (i.e. duration of response) and safety data of the patients
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Response and patient's clinical characteristics
Will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate (Responders vs Non-Responders). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
Event-free survival
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Overall survival
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

Full Information

First Posted
September 10, 2018
Last Updated
October 13, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03672539
Brief Title
Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome
Official Title
A Pilot Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Gemtuzumab Ozogamicin (GO) in Relapsed Refractory Patients With Acute Myeloid Leukemia (AML) and Post-Hypomethylating Agent (Post-HMA) Failure High-Risk Myelodysplastic Syndrome (HR-MDS)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 7, 2018 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial studies the side effects and how well liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin work in treating patients with acute myeloid leukemia that has come back (relapsed) or that does not respond to treatment (refractory) or high risk myelodysplastic syndrome. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine, 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 calicheamicin. Gemtuzumab ozogamicin attached to CD33 positive cancer cells in a targeted way and delivers calicheamicin to kill them. Giving liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin together may be an effective treatment for relapsed or refractory acute myeloid leukemia or high risk myelodysplastic syndrome.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety of liposome-encapsulated daunorubicin-cytarabine (liposomal cytarabine and daunorubicin [CPX-351]) in combination with gemtuzumab ozogamicin (GO) in relapsed refractory (R-R) patients with acute myeloid leukemia (AML) and post-hypomethylating agent (post-HMA) failure high-risk myelodysplastic syndrome (HR-MDS). II. To determine the efficacy of liposomal cytarabine and daunorubicin (CPX-351) in combination with gemtuzumab ozogamicin (GO) in relapsed refractory patients with acute myeloid leukemia (AML) and post-hypomethylating agent (post-HMA) failure high-risk myelodysplastic syndrome (HR-MDS). SECONDARY OBJECTIVE: I. To determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR) of 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. II. To determine the effect of the level of pre-treatment expression of CD33 with response to this combination. III. To determine the baseline CD33 genotype via CD33 polymorphism study, and its effect on response to this combination. IV. To determine the effect of this treatment combination on responding patients transitioning to hematopoietic stem cell transplantation (HSCT). V. To evaluate the effect of the treatment combination on Health Related Quality of Life (HRQoL) parameters. OUTLINE: INDUCTION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 of cycle 1 and days 1 and 3 of cycle 2 and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity. CONSOLIDATION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity. MAINTENANCE CYCLE: Patients receive gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 14 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, High Risk Myelodysplastic Syndrome, Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (CPX-351, gemtuzumab ozogamicin)
Arm Type
Experimental
Arm Description
INDUCTION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 of cycle 1 and days 1 and 3 of cycle 2 and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity. CONSOLIDATION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity. MAINTENANCE CYCLE: Patients receive gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Gemtuzumab Ozogamicin
Other Intervention Name(s)
Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Liposome-encapsulated Daunorubicin-Cytarabine
Other Intervention Name(s)
CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall response rate
Description
Will use the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia and Myelodysplasia. Will estimate the ORR for the combination treatment, along with the 95% credible interval.
Time Frame
Up to 56 days
Title
Incidence and severity of all adverse events assessed using Common Toxicity Criteria version 4.0
Time Frame
Up to 14 months
Secondary Outcome Measure Information:
Title
Demographic/clinical characteristics (i.e. duration of response) and safety data of the patients
Description
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Time Frame
Up to 14 months
Title
Response and patient's clinical characteristics
Description
Will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate (Responders vs Non-Responders). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
Time Frame
Up to 14 months
Title
Event-free survival
Description
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Time Frame
Up to 14 months
Title
Overall survival
Description
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Time Frame
Up to 14 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of CD33 positive (>= 3%), relapsed refractory acute myeloid leukemia by World Health Organization (WHO) criteria. Patients with post-hypomethylating agent (post-HMA) failure high-risk myelodysplastic syndrome (MDS), as defined by the presence of > 10% blasts, are also eligible. Patients with MDS or chronic myelomonocytic leukemia (CMML) who received hypomethylating agent based-therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless of any prior therapy for MDS or CMML. The WHO classification will be used for AML. Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2. 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 (b-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, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; abstinence. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug. Patients or their legally authorized representative must provide written informed consent. 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 or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, 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 active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV. 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 200 mg/m^2. Patients with uncontrolled, active infections (viral, bacterial, or fungal). Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV). Patients with liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse. Allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months before the start of protocol-specified therapy, or with 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. Patients must have recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment. 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. Prior treatment with CPX-351 or gemtuzumab ozogamicin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yesid Alvarado-Valero
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yesid Alvarado-Valero
Phone
713-794-4364
Email
yalvarad@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Yesid Alvarado-Valero

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome

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