CPX-351+GO in Subjects 55 Years Old, or Older, With AML

NCT03878927 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 1801018937
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label study to assess the safety and efficacy of CPX-351 in combination with gemtuzumab ozogamicin (GO) as first intensive therapy in older (age \>55 years) subjects with newly diagnosed AML who are eligible for intensive induction chemotherapy, or AML subjects who previously failed low-intensity therapy but who would be eligible for high-intensity chemotherapy, with companion cognitive function testing to determine whether this contributes to outcome in these subjects. Subjects may have received prior AML treatment with non-intensive regimens, e.g. hypomethylating agents, low-dose cytarabine, or lenalidomide or a clinical trial drug in combination with hypomethylating agents or low-dose cytarabine, but may not have received intensive AML treatment with anthracyclines and/or infusional cytarabine prior to enrollment on this trial. Subjects may not have been treated with GO or other antibody targeting CD 33 prior to enrollment on this trial. The cohort will include 30 subjects treated with the combination of CPX-351 and GO and is designed to establish the safety and feasibility of the combination. These subjects will be assessed for efficacy and safety. Quality of life will be assessed using the FACT-LEU in all subjects. Cognitive function will be assessed using the Blessed Orientation-Memory-Concentration Test and the Montreal Cognitive Assessment.

Conditions

Acute Myeloid Leukemia

Keywords

AML; De novo AML; Secondary AML; Therapy-related AML

Outcome Measures

Primary Outcomes (1)

• Feasible dose of Gemtuzumab Ozogamicin (GO) in combination with CPX-351 (cytarabine:daunorubicin) in older subjects with AML

  The combination of CPX-351 + GO will be declared feasible if at least one dose of GO (day 1, 4, and 7) at 3 mg/m\^2 can be safely delivered to subjects.

  5 years

Secondary Outcomes (8)

• Efficacy of the combination of CPX and GO as first intensive therapy in elderly (age ≥55 years) by response rate

  5 years

• Safety of the combination of CPX and GO in elderly (age ≥55 years) subjects with AML by evaluation of the frequency and severity of adverse events.

  5 years

• Assessment of Minimal Residual Disease (MRD) response in subjects treated with this combination using multiparameter flow cytometry and next generation sequencing.

  5 years

• Quality of Life Assessment using the Functional Assessment of Cancer Therapy-Leukemia (FACT-LEU).

  5 years

• Assessment of the relationship of cognitive function to outcome using the Blessed Orientation-Memory-Concentration Test

  5 years

Study Arms (3)

Cohort A

EXPERIMENTAL

CPX-351 : Daunorubicin 44mg/m\^2 and cytarabine 100mg/m\^2/day on Days 1,3 and 5 (90 minute IV infusion) Gemtuzumab ozogamicin: 3mg/m\^2/day on Day 1 (2 hour IV infusion)

Drug: CPX-351; Drug: Gemtuzumab Ozogamicin

Cohort B

EXPERIMENTAL

CPX-351: Daunorubicin 44mg/m\^2 and cytarabine 100mg/m\^2 on Days 1, 3 and 5 (90 minute IV infusion) Gemtuzumab ozogamicin: 3mg/m\^2 on Days 1, 4 (2 hour IV infusion)

Drug: CPX-351

Cohort C

EXPERIMENTAL

CPX-351: Daunorubicin 44mg/m\^2 and cytarabine 100mg/m\^2 on Days 1, 3, and 5 (90 minute IV infusion) Gemtuzumab ozogamicin: 3mg/m\^2 on Days 1, 4 and 7 (2 hour IV infusion)

Drug: CPX-351; Drug: Gemtuzumab Ozogamicin

Interventions

CPX-351 DRUG

CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio. The liposome membrane is composed of distearoylphosphatidylcholine, distearoylphosphatidylglycerol and cholesterol in a 7:2:1 molar ratio.

Also known as: Vyxeos

Cohort A; Cohort B; Cohort C

Gemtuzumab Ozogamicin DRUG

Gemtuzumab ozogamicin is a CD-33 directed antibody drug conjugated to calicheamicin. CD 33 is expressed on myeloid leukemic blast cells and on normal hematopoietic cells. The drug is approved for the treatment of newly diagnosed CD 33 positive AML in adults and the treatment of relapsed and refractory CD 33 positive AML in adults. The drug is available for injection 4.5 mg as a lyophilized cake or powder in a single use vial for reconstitution and dilution.

Also known as: Mylotarg

Cohort A; Cohort C

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and voluntarily give informed consent
• Age≥55 years at the time of study treatment
• Pathological diagnosis of AML according to WHO criteria (with \>20% blasts in the peripheral blood or bone marrow) including:
• De novo AML with intermediate or adverse-risk karyotypes (including subjects with karyotypic abnormalities characteristic of MDS), who may have received treatment with low-dose cytarabine, hypomethylating agents, and/or non-intensive chemotherapy-based clinical trial treatments
• Secondary AML: transformed from prior MDS or MPN, confirmed by bone marrow documentation of prior antecedent hematologic disorder
• Therapy-related AML: t-AML, requires documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease
• Performance status \>50% KPS, ECOG 0-2
• Laboratory values fulfilling the following:
• Peripheral blast count is less than 30,000/μL prior to administration of drug
• Serum creatinine \< 2.5 mg/dL
• Serum total bilirubin \< 2.5 mg/dL
• Serum alanine aminotransferase or aspartate aminotransferase \< 3 times the ULN
• Subjects with elevated liver enzymes and serum creatinine values secondary to AML are eligible after discussion with PI
• Cardiac ejection fraction ≥ 50% by echocardiography, MUGA, or Cardiac MRI
• Negative pregnancy test for non-menopausal women ≥ 55 years old

You may not qualify if:

• Acute promyelocytic leukemia \[t(15;17)\], AML with karyotype inversion 16 or t(8;21)
• Clinical or morphologic evidence of active CNS leukemia
• Prior intensive chemotherapy for AML with anthracycline/cytarabine-based regimens, GO or other antibody targeting CD33 as a single agent and/ or prior HSCT. Subjects may have been treated with commercially available or investigational hypomethylating agents (e.g. decitabine, azacitidine, SGI-110), lenalidomide, or low-dose cytarabine (not to exceed 20 mg/m2 daily for 14 days for ≤ 6 cycles) or on clinical trials with combinations of low-intensity chemotherapy agents. No more than one agent or combination of agents can be given for treatment of AML prior to enrollment onto this protocol.
• Prior treatment including HMA, systemic chemotherapy, surgery, or radiation therapy must have been completed at least 7 days before start of study treatment or after discussion with PI. Treatment with investigational agents must have been completed at least 14 days prior to study drug treatment. Hydroxyurea is permitted for control of blood counts before the start of study treatment. Toxicities associated with prior therapies must have recovered to grade 1 or less prior to start of study treatment.
• Subjects with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
• Subjects with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)
• Active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs.
• Subjects with current or recent evidence of invasive fungal infection (blood or tissue culture); subjects with recent fungal infection must have a subsequent negative cultures to be eligible
• Known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values)
• Hypersensitivity to cytarabine, daunorubicin or liposomal products
• History of Wilson's disease or other copper-metabolism disorder
• History of prior bone marrow or solid organ transplantation

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Jazz Pharmaceuticals: collaborator
• Pfizer: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (5)

• Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.

  PMID: 19880497 BACKGROUND

• Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2004:98-117. doi: 10.1182/asheducation-2004.1.98.

  PMID: 15561679 BACKGROUND

• Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH. Age and acute myeloid leukemia. Blood. 2006 May 1;107(9):3481-5. doi: 10.1182/blood-2005-09-3724. Epub 2006 Feb 2.

  PMID: 16455952 BACKGROUND

• Kantarjian H, O'brien S, Cortes J, Giles F, Faderl S, Jabbour E, Garcia-Manero G, Wierda W, Pierce S, Shan J, Estey E. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006 Mar 1;106(5):1090-8. doi: 10.1002/cncr.21723.

  PMID: 16435386 BACKGROUND

• Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. 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. J Clin Oncol. 2003 Dec 15;21(24):4642-9. doi: 10.1200/JCO.2003.04.036.

  PMID: 14673054 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ellen K Ritchie, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 18, 2019
• Study Start: August 23, 2019
• Primary Completion: August 15, 2022
• Study Completion: September 1, 2022
• Last Updated: March 10, 2023

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)