CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT02019069 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-28524NCI-2013-01982HEM0036P30CA124435
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Conditions

Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Response Rate (RR)

  The response rate was determined as the sum of complete response calculated by adding the total complete response (CR) and complete response with incomplete count recovery (CRi). The outcome is reported as the total number without dispersion. * CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC \> 1000/uL, with transfusion independence. * CRi = all the parameters for CR, but platelets \< 100,000/uL and/or ANC ≤ 1000/uL.

  Day 42

Secondary Outcomes (8)

• Complete Response With Incomplete Count Recovery (CRi)

  Day 42

• Complete Response (CR)

  Day 42

• Duration of Remission (DOR) Following Induction With CPX-351

  Up to 1 year

• Overall Survival (OS)

  At 12 months

• Early Induction Mortality (Day 30 After 1st Induction)

  30 days

Study Arms (1)

Liposomal cytarabine-daunorubicin CPX-351

EXPERIMENTAL

* 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. * 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. * CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.

Drug: liposomal cytarabine-daunorubicin CPX-351

Interventions

liposomal cytarabine-daunorubicin CPX-351 DRUG

Given IV

Also known as: CPX-351

Liposomal cytarabine-daunorubicin CPX-351

Eligibility Criteria

• Age: 60 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 ≥ 60
• Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and high risk MDS by IPSS) along with one of the following:
• Patients with de novo or secondary MDS with progression/refractoriness after HMA treatment who have not transformed to AML
• Patients with MDS and prior HMA treatment for MDS who transform to AML
• Patients with AML who are refractory/relapsed after HMA therapy for their AML are eligible
• Life expectancy \> 1 month
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Able to adhere to the study visit schedule and other protocol requirements
• Laboratory values fulfilling the following:
• Serum creatinine \< 2.0 mg/dL
• Serum total bilirubin ≤ 2.5 mg/dL. Note, patients with Gilbert's syndrome may have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their baseline total bilirubin.
• Serum alanine aminotransferase or aspartate aminotransferase \< 3 times ULN
• Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography) or MUGA scan
• Patients with second malignancies may be eligible at discretion of PI given acute life threatening nature of untreated AML or higher risk MDS. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible.

You may not qualify if:

• Patients who have previously undergone allogeneic hematopoietic stem cell transplant will be excluded from this study
• Patients who have previously had \> 368 mg/m2 cumulative dose of daunorubicin or \> 368 mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment of solid tumors). See appendix for anthracycline equivalence table.
• Acute promyelocytic leukemia \[t(15;17)\]
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
• Patients who have had conventional intensive cytotoxic induction chemotherapy for treatment of specifically MDS or AML are excluded.
• Patients who have not previously been treated with HMA therapy will be excluded
• Clinical evidence of active CNS leukemia
• Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)
• Active and uncontrolled infection. Patients with an active infection receiving treatment and hemodynamically stable for 48 hours may be entered into the study
• Known active uncontrolled HIV or hepatitis C infection
• Known hypersensitivity to cytarabine, daunorubicin or liposomal products
• Known history of Wilson's disease or other copper-related disorders
• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation
• Laboratory abnormalities:
• Serum creatinine ≥ 2.0 mg/dL

Sponsors & Collaborators

• Rondeep Brar: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Rondeep Singh Brar
• Organization: Stanford University

rbrar@stanford.edu

(650) 498-6000

Study Officials

• Rondeep Brar, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 24, 2013
• Study Start: February 3, 2014
• Primary Completion: December 4, 2017
• Study Completion: December 18, 2017
• Last Updated: January 22, 2019
• Results First Posted: January 15, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)