Clofarabine, Idarubicin, Cytarabine, Vincristine Sulfate, and Dexamethasone in Treating Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia

Mixed Phenotype Acute Leukemia Clinical Trial

Official title:

A Phase 2 Study of Clofarabine, Idarubicin, Cytarabine, Vincristine, and Corticosteroids for Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02135874
• Other study ID #: 2013-0073
• Secondary ID: NCI-2014-0232220
• Status: Completed
• Phase: Phase 2
• Start date: October 27, 2014
• Est. completion date: February 21, 2023

Study information

• Verified date: March 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well clofarabine, idarubicin, cytarabine, vincristine sulfate, and dexamethasone work in treating patients with mixed phenotype acute leukemia that is newly diagnosed or has returned after a period of improvement (relapsed). Drugs used in chemotherapy, such as clofarabine, idarubicin, cytarabine, vincristine sulfate, and dexamethasone, work 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.

Description:

PRIMARY OBJECTIVE:

I. To evaluate the response rate of the chemotherapy regimen in patients with mixed phenotype acute leukemia.

SECONDARY OBJECTIVE:

I. To evaluate the durability of response, the overall and event-free survival rates, and the safety profile of the regimen.

OUTLINE:

INDUCTION THERAPY: Patients receive clofarabine intravenously (IV) over 60 minutes on days 1-4 or 1-3; idarubicin IV over 30-60 minutes on days 1-3 or 1-2; cytarabine IV over 2 hours on days 1-4; vincristine sulfate IV over 15-30 minutes on days 1, 8, and 15; and dexamethasone IV over 10-30 minutes on days 1-4 and 15-18. Patients with a certain type of leukemia may receive rituximab IV over 4-6 hours on days 1 and 8 or sorafenib tosylate orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Patients receive clofarabine IV over 60 minutes on days 1-3 or 1-2; idarubicin IV over 30-60 minutes on days 1-2; cytarabine IV over 2 hours on days 1-3 or 1-2; vincristine sulfate IV over 15-30 minutes on days 1, 8, and 15; and dexamethasone IV over 10-30 minutes on days 1-4 and 15-18. Patients with a certain type of leukemia may receive rituximab IV over 4-6 hours on days 1 and 8 of cycles 1-3 or sorafenib tosylate PO BID on days 1-28 of cycle 1-6 and beyond. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Sign an informed consent document

• Newly diagnosed or relapsed mixed phenotype acute leukemia (MPAL), which for this protocol, will be defined as follows: bone marrow result interpreted by the reading pathologist (or tissue biopsy for cases of extramedullary disease) as: biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population

• Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 at study entry

• Adequate organ function as outlined below (unless due to leukemia)

• Serum creatinine =< 3 mg/dL

• Total bilirubin =< 2.5 mg/dL

• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and/or aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper limit of normal (ULN) or =< 5 x ULN if related to disease

• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days; women of childbearing potential and men must agree to use contraception at study entry and for the duration of active study treatment

• Cardiac ejection fraction >= 40% (by either cardiac echocardiogram [echo] or multi gated acquisition [MUGA] scan); documentation of recent (=< 6 months from screening) outside reports is acceptable

• If newly diagnosed, prior therapy with hydrea and/or steroid and the use of a single or a two day dose of cytarabine (up to 3 g/m^2), for emergency use up to 24 hours prior to start of study therapy is allowed

Exclusion Criteria:

• Breast feeding females

• Patients with active, uncontrolled infections

• Patients with active secondary malignancy will not be eligible unless approved by the principal investigator

Related Conditions & MeSH terms

• Acute Bilineal Leukemia
• Acute Biphenotypic Leukemia
• Acute Disease
• Acute Leukemia of Ambiguous Lineage
• Acute Undifferentiated Leukemia
• Leukemia
• Leukemia, Biphenotypic, Acute
• Mixed Phenotype Acute Leukemia
• Mixed Phenotype Acute Leukemia, B/Myeloid, Not Otherwise Specified
• Mixed Phenotype Acute Leukemia, T/Myeloid, Not Otherwise Specified
• Recurrent Mixed Phenotype Acute Leukemia

Intervention

Drug:
• Clofarabine
Given IV
• Cytarabine
Given IV
• Dexamethasone
Given IV
• Idarubicin
Given IV

Biological:
• Rituximab
Given IV

Drug:
• Sorafenib
Given PO
• Sorafenib Tosylate
Given PO
• Vincristine
Given IV
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants Complete Response	Response is Complete Response (CR) is Neutrophil count >/= 1.0 x 10^9/L, . Platelet count >/= 100 x 10^9/L, Bone marrow aspirate < 5% blasts, No extramedullary leukemia.	Up to 2 months
Secondary	4-week Mortality Rate	Number of participants who died after 4 weeks of treatment.	At 4 weeks

External Links

•   MD Anderson Cancer Center Website