CPX-351 and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Acute Myeloid Leukemia

NCT03904251 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 18-001419NCI-2019-00701
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 5

Brief Summary

This phase Ib trial studies the best dose of gemtuzumab ozogamicin when given together with CPX-351 in treating patients with acute myeloid leukemia that has come back after it was previously in remission. CPX-351 is a chemotherapy, which works in different ways to stop the growth of cancer 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 chemotherapy called calicheamicin. Gemtuzumab attaches to CD33 (transmembrane receptor) positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving CPX-351 and gemtuzumab ozogamicin may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.

Conditions

Acute Myelogenous Leukemia

Keywords

AML, Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  MTD is defined as the cohort of participants one cohort below the cohort that develop dose-limiting toxicity (DLT) in at least 2 participants.

  Up to day 42

Secondary Outcomes (7)

• Objective response rate (ORR)

  Up to day 42

• Proportion of participants who go on to receive allogeneic hematopoietic cell transplantation (HSCT) after achieving CR/CRi

  Up to 18 months

• Duration of remission

  Up to 18 months

• Incidence of toxicities

  Up to day 42

• Diagnosis of veno-occlusive disease (VOD)

  Up to 18 months

Other Outcomes (5)

• Genotype at CD33 splicing single nucleotide polymorphism (SNP) RS12459419

  Up to 18 months

• Multidrug resistance activity of leukemia cell P-glycoprotein (Pgp)

  Up to 18 months

• Multidrug resistance activity of leukemia cell multidrug resistance protein 1 (MRD1)

  Up to 18 months

Study Arms (1)

Treatment (CPX-351, gemtuzumab ozogamicin)

EXPERIMENTAL

INDUCTION: Patients receive liposome-encapsulated daunorubicin 44mg/m2 - cytarabine 100mg/m2 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin 3 mg/m2 (max 4.5 mg) IV over 120 minutes on day 7, or days 4 and 7, or days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR/CRi receive consolidation therapy at the discretion of the treating physician and/or proceed to allogeneic HSCT.

Drug: Gemtuzumab Ozogamicin; Drug: Liposome-encapsulated Daunorubicin-Cytarabine

Interventions

Gemtuzumab Ozogamicin DRUG

Given IV

Also known as: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676

Treatment (CPX-351, gemtuzumab ozogamicin)

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Also known as: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos

Treatment (CPX-351, gemtuzumab ozogamicin)

Eligibility Criteria

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

You may qualify if:

• Bone marrow blasts \>= 5% that develops after remission, no restriction on prior number of relapses or regimens
• Eastern Cooperative Oncology Group (ECOG) 0-2
• At least a 3-month duration of remission prior to relapse
• Participants with relapse after allogeneic transplantation are included
• Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must be discontinued at least 14 days prior to start of salvage induction
• Serum total bilirubin =\< 2.0 mg/dL, unless considered due to Gilbert?s disease or leukemia involvement
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 times the upper limit of normal, unless considered due to leukemia involvement
• Alkaline phosphatase =\< 3 times the upper limit of normal, unless considered due to leukemia involvement
• Serum creatinine =\< 2.0 mg/dL, or creatinine clearance \> 40 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
• Ability to give full informed consent on their own
• Females of reproductive potential (postmenopausal for less than 24 consecutive months) must have a negative pregnancy

You may not qualify if:

• Currently receiving targeted therapy for FLT3 (cytokine receptor tyrosine kinase class III), IDH1, or IDH2 (isocitrate dehydrogenase, 1, 2) mutations and intent to continue use; prior use of targeted therapy for such mutations is allowed, but agents should be discontinued 1 week prior to enrollment
• Acute promyelocytic leukemia
• Second malignancy that would limit survival by less than 2 years
• New York Heart Association class III or VI
• Left ventricular ejection fraction \< 50%
• History of coronary stent placement that requires mandatory continuation of dual-antiplatelet therapy
• History of Wilson?s disease or other copper handling disorders
• Hypersensitivity to cytarabine, daunorubicin, or liposomal products
• Active invasive fungal infection
• Active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
• Lifetime cumulative daunorubicin-equivalent anthracycline dose \> 368 mg/m\^2

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Pfizer: collaborator
• Jazz Pharmaceuticals: collaborator
• University of California, Los Angeles: collaborator

Study Sites (5)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Related Publications (1)

• Jentzsch M, Grimm J, Bill M, Brauer D, Backhaus D, Goldmann K, Schulz J, Niederwieser D, Platzbecker U, Schwind S. ELN risk stratification and outcomes in secondary and therapy-related AML patients consolidated with allogeneic stem cell transplantation. Bone Marrow Transplant. 2021 Apr;56(4):936-945. doi: 10.1038/s41409-020-01129-1. Epub 2020 Nov 19.

  PMID: 33208914 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

Gemtuzumab; CPX-351; Injections; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; 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; Drug Administration Routes; Drug Therapy; Therapeutics; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Caspian Oliai, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 5, 2019
• Study Start: July 18, 2019
• Primary Completion: October 25, 2023
• Study Completion: October 25, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

US (5)