Proteasome Inhibition in Acute Promyelocytic Leukemia

Brief Title

Proteasome Inhibition in Acute Promyelocytic Leukemia

Official Title

Phase II Study to Evaluate the Role of Bortezomib in the Management of Relapsed Acute Promyelocytic Leukemia

Brief Summary

      The clinical outcome of relapsed acute promyelocytic leukemia (APL) is poor with current
      standard of care approaches. Additionally, standard of care warrants an autologous stem cell
      transplant to be done once molecular remission is achieved. Unfortunately, the majority of
      our patients cannot afford this procedure. We have previously reported the clinical outcome
      of relapsed patients who were managed without a stem cell transplants and showed that the
      event free survival at 5 years is less than 35%. Pre-clinical data reported from our
      laboratory demonstrates that there is significant synergy between arsenic trioxide (ATO;
      which is the accepted standard of care agent for relapsed APL) and Bortezomib (a proteasome
      inhibitor). We have evaluated this combination extensively in-vitro and this data was
      accepted as an oral presentation at the American Society of Hematology (ASH) meeting in 2011.
      More recently we have also reported the potential mechanism for this synergy (Poster at ASH
      2012). We also have mouse model data which supports these findings. We plan to move this
      combination of ATO based therapy combined with Bortezomib to a Phase II clinical trial to
      validate these observations. The anticipated potential is that we will have a combination
      therapy that is less expensive, cost effective and safe with comparable clinical outcomes to
      those treated with the more expensive standard of care which includes an autologous stem cell
      transplant and which the majority of our patients cannot afford.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Safety

Secondary Outcome

 Efficacy

Condition

Relapsed Acute Promyelocytic Leukemia

Intervention

Bortezomib

Study Arms / Comparison Groups

 Bortezomib in treatment

Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

30

Start Date

May 2013

Completion Date

May 2018

Primary Completion Date

May 2018

Eligibility Criteria

        Inclusion Criteria:

        i. Diagnosis of relapsed t(15;17)(PML-RARα) positive APL confirmed by reverse transcriptase
        polymerase chain reaction (RT-PCR).

        ii. Normal cardiac function with normal electrocardiogram (QTc less than 500 msec) within
        48 hours of study entry.

        iii. Patient or guardian willing to give informed consent / assent. Must not have a
        psychiatric disorder(s) that would interfere with consent, study participation, or
        follow-up.

        iv. Patients may have received hydroxyurea, 48 hours or less of all trans retnoic acid
        (ATRA), and 1 dose of an anthracycline and still be eligible for participation in this
        study.

        v. Life expectancy of at least 2 weeks after entry on study. vi. No age limit for entry
        into study. vii. ECOG performance score 0, 1, or 2. viii. Fertile patients must agree to
        use an effective barrier method of contraception (e.g., latex condom, diaphragm, or
        cervical cap) to avoid pregnancy while on therapy and for 3 years following the
        discontinuation of therapy.

        ix. Have a negative serum or urine pregnancy test prior to the first dose of therapeutic
        drugs (if patient is a female of childbearing potential). If breast feeding they should be
        willing to stop breast feeding.

        Exclusion Criteria:

        i. Intracranial bleed at diagnosis. ii. ECOG performance score 3 and above. iii. Severe
        uncontrolled infection, fulminant sepsis at diagnosis or documented pneumonia.

        iv. History of cardiac arrhythmia; symptomatic coronary heart disease; uncontrollable
        arterial hypertension (diastolic blood pressure > 115 mm Hg); severe psychiatric disease or
        other concomitant diseases which do not comply with the criteria for the participation in
        the study.

        v. Acute hepatitis (Bilirubin ≥ 5mg% or liver enzymes ≥ 4 times above laboratory normal
        value) vi. Acute renal failure or serum creatinine ≥ 2 mg% not reversed by hydration. vii.
        Patients suffering from an additional malignant tumor. No past history of receiving therapy
        for another malignancy, apart from squamous cell carcinoma or basal cell carcinoma of the
        skin.

        viii. Pregnancy or lactation. ix. Patients with proven intolerance to the study drugs x.
        Inability, missing willingness or anticipated lack of compliance by the PI to participate
        in the study. Must not have any other severe concurrent disease and/or uncontrolled medical
        conditions, which, in the judgment of the investigator, could predispose patients to
        unacceptable safety risks or compromise compliance with the protocol.
      

Gender

All

Ages

1 Year - 75 Years

Accepts Healthy Volunteers

No

Contacts

, 91-416-2282891, [email protected]

Location Countries

India

Location Countries

India

NCT ID

NCT01950611

Organization ID

IRB 8225 27/02/13

Responsible Party

Principal Investigator

Study Sponsor

Christian Medical College, Vellore, India

Study Sponsor

, , 

Verification Date

September 2013