Bendamustine Hydrochloride and Idarubicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia or Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01141725
First received: June 9, 2010
Last updated: December 7, 2012
Last verified: December 2012

June 9, 2010
December 7, 2012
September 2010
November 2012   (final data collection date for primary outcome measure)
  • Maximum tolerated dose (MTD) of bendamustine hydrochloride (Phase I) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    The highest dose level at which no more than one patient out of 6 experiences dose-limiting toxicities (DLT). DLT consists of grade 3-4 non-hematologic toxicity, with the exception of drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting, and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin that recovers to < grade 2 by 7 days.
  • Response (Phase II) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assessed by cytogenetics/fluorescence in situ hybridization (FISH) and flow cytometry of blood and bone marrow samples. The response criteria defined by Cheson et al. will be used in this study. These criteria are: morphologic leukemia-free state; morphologic complete remission (CR); cytogenetic CR (CRc); molecular CR (CRm); morphologic CR with incomplete blood count recovery (CRi); partial remission (PR); treatment failure; recurrence (progressive disease).
  • Incidence of greater than or equal to grade 3 toxicity [ Time Frame: Through day +100 after end of therapy or until the patient received an alternative treatment for leukemia, whatever happens earlier ] [ Designated as safety issue: Yes ]
    Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0.
  • Maximum tolerated dose of bendamustine hydrochloride (for the entire study) [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]
    Cohorts of 3 patients will be assessed for both toxicity (<30% grade 3-4 non hematologic) and response (>40% CR). If parameters are met Bendamustine dose will be escalated to the next higher dose. There are 4 dosing stages, and more than 1 cohort of 3 patients may be needed to fully determine outcome prior to escalation. We estimate 2-3 months per cohort, therefore conservative estimate is that in 16 months of this 24 month study, dose escalation element of the study will be complete.
  • Complete response rate (on a per patient basis) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    For each patient treated, CR will be measured during the first and second cycles. IF the patient fails to achieve CR in the first cycle, they may continue to receive a 2nd cycle. If a patient fails to achieve CR by the end of the 2nd cycle, the patient will move on to alternatives to this therapy. Therefore the CR rate per patient will be completely determined by the 8 weeks, the time required for 2 cycles to be administered and followed. For the entire study, the CR rate will be determined only after the final patient has been treated. Therefore study CR rate time frame is 27 months.
  • Toxicity [ Time Frame: 4 weeks per patient ] [ Designated as safety issue: Yes ]
    For each patient treated, toxicity will be measured during each of the three possible cycles. Initial dose limiting toxicity will be determined within 4 weeks of each bendamustine dose cycle. The acute toxicity in each patient therefore will be expected to be completely assessed 28 days after their final bendamustine dose cycle, in their 1st, 2nd, or 3rd cycle, depending. For the entire study, the toxicity rate will be determined only after the final patient has been treated. Therefore the study toxicity assessment time frame is 27 months.
Complete list of historical versions of study NCT01141725 on ClinicalTrials.gov Archive Site
  • Disease free survival (DFS) [ Time Frame: Over 5 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Over 5 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: 36 months following final patient treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 36 months following final patient treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Bendamustine Hydrochloride and Idarubicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia or Myelodysplastic Syndrome
Safety and Clinical Activity of Treanda® (Bendamustine HCL) and Idarubicin in Combination Therapy for Patients Age >= 50 With Previously Untreated Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome

This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride when given together with idarubicin in treating older patients with previously untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Drugs used in chemotherapy, such as bendamustine hydrochloride or idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells

PRIMARY OBJECTIVES:

I. The maximum tolerated dose (MTD) that is associated with a complete remission (CR) rate of at least 40%, and a rate of grade 3-4 extramedullary toxicity < 30% in patients aged 50 or older with previously untreated AML or high-risk MDS.

SECONDARY OBJECTIVES:

I. The disease-free survival (DFS), and overall survival (OS) after therapy at each level of the dosing strategy.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study.

Patients receive bendamustine hydrochloride intravenously (IV) on days 1-5 and idarubicin IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually thereafter for 3 years.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • de Novo Myelodysplastic Syndromes
  • Myelodysplastic Syndrome With Isolated Del(5q)
  • Untreated Adult Acute Myeloid Leukemia
  • Drug: bendamustine hydrochloride
    Given IV
    Other Names:
    • bendamustin hydrochloride
    • bendamustine
    • cytostasan hydrochloride
    • Treanda
  • Drug: idarubicin
    Given IV
    Other Names:
    • 4-demethoxydaunorubicin
    • 4-DMDR
    • DMDR
    • IDA
Experimental: Treatment (combination chemotherapy)
Patients receive bendamustine hydrochloride IV on days 1-5 and idarubicin IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: bendamustine hydrochloride
  • Drug: idarubicin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
39
Not Provided
November 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of untreated AML or MDS with 10-19% marrow blasts; patients may be enrolled if they received prior treatment with demethylating agents specifically for the purpose of treating MDS or if they have received a single dose of cytarabine for the control of symptoms related to AML
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Serum creatinine =< 2.0 mg/dL; if serum creatinine > 2.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
  • Males should be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
  • Women must be postmenopausal or must be willing to use an acceptable method of contraception to avoid pregnancy for the entire period of the study and for at least 3 months after the study; a postmenopausal woman is defined as a woman who has experienced amenorrhea > 12 consecutive months or a woman on hormone replacement therapy with documented follicle-stimulating hormone (FSH) level > 35 mIU/mL; for patients in whom menopausal state is in question, a negative pregnancy test will be required prior to enrollment

Exclusion Criteria:

  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea or single-dose cytarabine; subjects who are enrolled with high risk MDS (specifically) may have prior treatment with drugs in the class called "demethylating agents"; examples of these drugs include 5-azacytidine (azacitidine) and 5-azadeoxycytidine (decitabine), and may include approved or experimental drugs not currently used, which fall into this class and may be developed in the future; the patient must have recovered from all acute toxicities from any previous therapy
  • Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
  • Pregnant or lactating patients
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
  • Known hypersensitivity to bendamustine (bendamustine hydrochloride) or idarubicin
  • Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)
  • Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy
  • Other circumstances in which patients with prior malignancies are not excluded, include the following:

    • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, if definitive treatment for the condition has been completed
    • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed
    • Concurrent hormonal therapy is allowed
Both
50 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01141725
2413.00, NCI-2010-01253, K12CA076930
No
Pagel, John, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
National Cancer Institute (NCI)
Principal Investigator: John Pagel Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP