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Trial record 32 of 441 for:    "Juvenile myelomonocytic leukemia"

Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL

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ClinicalTrials.gov Identifier: NCT02147873
Recruitment Status : Terminated (Study terminated due to lack of efficacy)
First Posted : May 28, 2014
Last Update Posted : October 20, 2016
Sponsor:
Information provided by (Responsible Party):
TetraLogic Pharmaceuticals

Brief Summary:
This is a randomized double blind placebo controlled study of azacitidine with or without birinapant in subjects with higher risk Myelodysplastic syndrome, secondary MDS or myelomonocytic leukemia (CMMoL) who are naïve, to azacitidine therapy. Pre-clinical and mechanistic studies support that azacitidine may modulate pathways that enable birinapant-mediated anti-tumor activity.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML) Drug: birinapant Drug: Azacitidine Drug: Placebo Phase 2

Detailed Description:

This is a randomized double blind placebo controlled study of azacitidine with or without birinapant in subjects with higher risk Myelodysplastic syndrome, secondary MDS or myelomonocytic leukemia (CMMoL)

The primary purpose of this study is :

-To compare the relative effect of azacitidine plus birinapant versus azacitidine plus placebo on response rate in patients with higher-risk MDS, secondary MDS or CMMoL.

The secondary purpose of this study is to compare effect of azacitidine plus birinapant relative to azacitidine with placebo on:

  • Hematologic improvement
  • Relapse free survival
  • Time to respond
  • Change in transfusion requirements
  • Duration of response
  • Overall survival
  • Adverse events

The exploratory objective of this study is to assess exploratory translational biomarkers for antitumor effects.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Azacitidine With or Without Birinapant With a Single Arm Open-Label Run-In Phase in Subjects With Higher Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Study Start Date : June 2014
Actual Primary Completion Date : January 2016
Actual Study Completion Date : June 2016


Arm Intervention/treatment
Active Comparator: azacitidine with birinapant
Azacitidine 75 mg/m2 IV on days 1-5, 8 & 9 OR days 1-7 and birinapant 13 mg/m2 IV twice a week (days 1 & 4) for 3 out of 4 weeks
Drug: birinapant
Other Name: TL32711

Drug: Azacitidine
Placebo Comparator: Azacitidine and placebo
Azacitidine 75mg/m2 IV days 1-5, 8 & 9 OR days 1-7 and placebo IV twice a week (days 1 & 4) for 3 out of 4 weeks
Drug: Azacitidine
Drug: Placebo



Primary Outcome Measures :
  1. Response Rate [ Time Frame: participants will be followed for until disease progression an expected average of 1 year ]

Secondary Outcome Measures :
  1. Hematologic improvement [ Time Frame: participants will be followed for until disease progression an expected average of 1 year ]
  2. Relapse free survival [ Time Frame: An expected average of 2 year post last study dose ]
    According to modified IWG 2006 criteria

  3. Time to respond [ Time Frame: participants will be followed for until disease progression an expected average of 1 year ]
  4. Change in transfusion requirements [ Time Frame: participants will be followed for until disease progression an expected average of 1 year ]
  5. duration of response [ Time Frame: participants will be followed for until disease progression an expected average of 1 year ]
    According to modified IWG 2006 criteria

  6. overall survival [ Time Frame: An expected average of 2 year post last study dose ]
  7. Adverse events profile [ Time Frame: participants will be monitored for adverse events throughout the treatment period and during follow up period ]

Other Outcome Measures:
  1. exploratory translational biomarkers for antitumor effect [ Time Frame: 30 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

key Inclusion Criteria:

  • Morphologically confirmed diagnosis of MDS/CMMoL according to FAB or WHO classification, including RAEB-t and MDS/MPN
  • International prognostic score-revised (IPSS-R) of >3.5 (Intermediate, High or Very High)
  • Previously untreated with hypomethylating agents for MDS/CMMoL
  • Performance status of 0, 1 or 2 by the ECOG scale
  • Adequate renal and liver function
  • Female subjects of childbearing potential must have a negative serum pregnancy test at screening within 96 hours prior to the first study dose.
  • Female subjects of childbearing potential and male subjects with partners of childbearing potential should ensure use of a highly effective method of birth control as defined by the investigator, for example, those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly during the study and for a period of 3 months following the last dose of any drug administered during the study.

Key Exclusion Criteria:

  • Relapsed or refractory to hypomethylating agents
  • Acute myeloid leukemia (AML), except those patients with RAEB-t who are not candidates for intensive AML therapy.
  • Participated in any interventional study within 4 weeks of randomization or 5 half lives (whichever is longer).
  • Received any hematopoietic growth factors within 14 days prior to screening.
  • Prior malignancy or secondary malignancy within the prior 2 years (except in situ cervical cancer, squamous cell carcinoma or basal cell carcinoma of the skin).
  • known diagnosis of human immunodeficiency virus or chronic active Hep B or C.
  • Uncontrolled hypertension
  • Impaired cardiac function, uncontrolled cardiac arrhythmias despite medications, or clinically significant cardiac disease
  • Lack of recovery of prior adverse events to Grade ≤1 severity (National Cancer Institute Common Terminology Criteria for Adverse Events version 4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.
  • Nursing or pregnant.
  • Known allergy or hypersensitivity to any of the formulation components
  • Any concurrent disease and/or medical condition that, in the opinion of the Investigator, would prevent the subject's participation.
  • History of cranial nerve palsy.
  • Being treated with anti-TNF therapies or has been treated with an anti-TNF therapy within 5 half-lives of randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02147873


  Show 76 Study Locations
Sponsors and Collaborators
TetraLogic Pharmaceuticals

Responsible Party: TetraLogic Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02147873     History of Changes
Other Study ID Numbers: TL32711-RAN-0094-PTL
2014-001719-37 ( EudraCT Number )
First Posted: May 28, 2014    Key Record Dates
Last Update Posted: October 20, 2016
Last Verified: October 2016

Keywords provided by TetraLogic Pharmaceuticals:
chronic myelomonocytic leukemia
MDS
CMML
myelodysplastic syndrome
TL32711
TL32711-0094
azacitidine
birinapant
higher risk
naive
double blind
placebo
placebo controlled
randomized

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors