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

Primary Purpose

Acute Bilineal Leukemia, Acute Biphenotypic Leukemia, Acute Leukemia of Ambiguous Lineage

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clofarabine
Cytarabine
Dexamethasone
Idarubicin
Rituximab
Sorafenib
Sorafenib Tosylate
Vincristine
Vincristine Sulfate
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 Bilineal Leukemia

Eligibility Criteria

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

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (combination chemotherapy)

Arm Description

See Detailed Description.

Outcomes

Primary Outcome Measures

Response (complete response or overall response rate)
The two groups of patients (newly diagnosed or relapsed/refractory) will be evaluated separately. The posterior response rate and their 95% credible intervals will be estimated.

Secondary Outcome Measures

4-week mortality rate (Newly diagnosed patients)
For discrete or categorical data, descriptive statistics will include tabulations of frequencies. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed.
Incidence of toxicity (Newly diagnosed patients)
Will be defined as any grade 3 or greater clinically significant non-hematological toxicity related to treatment. Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. For discrete or categorical data, descriptive statistics will include tabulations of frequencies.
4-week mortality rate (Relapsed patients)
Incidence of toxicity (Relapsed patients)
Will be defined as any grade 3 or greater clinically significant non hematological toxicity related to treatment. Graded according to NCI CTCAE version 4.0.

Full Information

First Posted
May 8, 2014
Last Updated
September 1, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02135874
Brief Title
Clofarabine, Idarubicin, Cytarabine, Vincristine Sulfate, and Dexamethasone in Treating Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia
Official Title
A Phase 2 Study of Clofarabine, Idarubicin, Cytarabine, Vincristine, and Corticosteroids for Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
October 27, 2014 (Actual)
Primary Completion Date
February 21, 2023 (Actual)
Study Completion Date
February 21, 2023 (Actual)

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 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Bilineal Leukemia, Acute Biphenotypic Leukemia, Acute Leukemia of Ambiguous Lineage, Acute Undifferentiated Leukemia, 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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Treatment (combination chemotherapy)
Arm Type
Experimental
Arm Description
See Detailed Description.
Intervention Type
Drug
Intervention Name(s)
Clofarabine
Other Intervention Name(s)
Clofarex, Clolar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Other Intervention Name(s)
4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
BA4 43 9006, BAY 43-9006, Bay-439006
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Sorafenib Tosylate
Other Intervention Name(s)
BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
LEUROCRISTINE, VCR, Vincrystine
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vincristine Sulfate
Other Intervention Name(s)
Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Response (complete response or overall response rate)
Description
The two groups of patients (newly diagnosed or relapsed/refractory) will be evaluated separately. The posterior response rate and their 95% credible intervals will be estimated.
Time Frame
Up to 2 months
Secondary Outcome Measure Information:
Title
4-week mortality rate (Newly diagnosed patients)
Description
For discrete or categorical data, descriptive statistics will include tabulations of frequencies. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed.
Time Frame
At 4 weeks
Title
Incidence of toxicity (Newly diagnosed patients)
Description
Will be defined as any grade 3 or greater clinically significant non-hematological toxicity related to treatment. Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. For discrete or categorical data, descriptive statistics will include tabulations of frequencies.
Time Frame
Up to 4 weeks after completion of study treatment
Title
4-week mortality rate (Relapsed patients)
Time Frame
At 4 weeks
Title
Incidence of toxicity (Relapsed patients)
Description
Will be defined as any grade 3 or greater clinically significant non hematological toxicity related to treatment. Graded according to NCI CTCAE version 4.0.
Time Frame
Up to 4 weeks after completion of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elias Jabbour
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

12. IPD Sharing Statement

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

Learn more about this trial

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

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