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Acute Lymphoblastic LeukemiaPhase 1NCT01110473

ABT-348 as Monotherapy and in Combination With Azacitidine to Treat Advanced Hematologic Malignancies

A Phase 1 study testing ABT-348 and ABT-348 and azacitidine in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by AbbVie (prior sponsor, Abbott) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the safety, pharmacokinetics and maximum tolerated dose of ABT-348 as monotherapy and when given in combination with azacitidine. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ABT-348 and ABT-348 and azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
3 sitesUnited States
Study dates
Apr 2010to Jun 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological or cytological confirmation of one of the following (Arms A, B and D):
  • Relapsed or refractory acute myelogenous leukemia (AML), untreated AML in subjects who are > 60 years of age and do not have favorable cytogenetics (i.e., lack t(8,21) or inv(16)/t(16,16) or acute lymphoblastic leukemia (ALL) in subjects who have failed or are unsuitable for standard therapy.
  • Chronic myelogenous leukemia (CML) subjects that have not responded or relapsed on imatinib and failed second line Tyrosine Kinase Inhibitor (TKI) therapy and are not a candidate for allogeneic bone marrow transplant.
  • B-cell chronic lymphocytic leukemia (CLL) subjects that have not responded or relapsed on fludarabine or in the opinion of the Principal Investigator are unsuitable for fludarabine therapy and have not responded to or relapsed on alkylating therapy.
  • Myelodysplasia (MDS) including chronic myelomonocytic leukemia (CMML) subjects with International Prognostic Scoring System (IPSS) risk categories of Intermediate-2 (INT-2) or High risk, or any myelodysplasia with symptomatic anemia resistant to erythropoietin, immunosuppressant, or DNA methyltransferase inhibitor therapy (e.g., azacitidine/decitabine).
  • 1a. Histological or cytological confirmation of one of the following (Arm C):
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  • Relapsed or refractory AML, untreated AML in subjects who are > 60 years of age and do not have favorable cytogenetics (i.e., lack t(8,21).
  • Untreated MDS including CMML with IPSS risk categories of INT-2 or High risk or with more than 10% blasts in the bone marrow, or any myelodysplasia with symptomatic anemia resistant to erythropoietin, or immunosuppressant, or subject has no response after four cycles of DNA methyltransferase inhibitor therapy or subject has progressed on DNA methyltransferase inhibitor therapy.
  • Eastern Cooperative Oncology Group Status of 0-2
  • Hematologic function for subjects with CLL and CML demonstrated by hemoglobin > 9 g/dL, platelets > 100,000/µL, ANC > 1500/mm3
  • Serum creatinine value of ≤ 1.8 times the upper limit of normal (ULN) and either an estimated creatinine clearance value as determined by the Cockcroft-Gault formula or based on a 24 hour urine collection creatinine clearance value of ≥ 50 mL/min
  • Adequate liver function as demonstrated by serum bilirubin < 2 x ULN and AST and ALT < 2.5 x ULN
  • QTc interval < 500 msec
  • Left Ventricular Ejection Fraction > 50%
  • Women of child-bearing potential and men must agree to use adequate contraception prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy.
  • Capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures.

Who cannot join

  • Subject has known active CNS involvement. The subject has untreated brain or meningeal metastases.
  • ALL or AML subject has received acute anti-cancer therapy within 14 days prior to Study Day 1
  • CML, CLL or myelodysplasia (MDS) subjects has received acute anti-cancer therapy within 28 days or biologic therapy within 6 weeks prior to Study Day 1. Per Investigator discretion, hydroxyurea may be used anytime during the study. Tyrosine kinase inhibitors may not be administered 7 days prior to Study Day 1.
  • Subjects with poorly controlled diabetes mellitus
  • Subject has unresolved toxicities from prior anti-cancer therapy, grade 2 or higher clinically significant toxicity (excluding alopecia)
  • Subject has had major surgery within 28 days prior to Study Day 1
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  • Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg
  • Subject has proteinuria grade > 1
  • Subject is unable to swallow or absorb oral tablets normally
  • Subject is receiving therapeutic anticoagulation therapy. Low-dose anticoagulation (e.g., low-dose heparin or warfarin) for catheter prophylaxis will be allowed
  • Subject has infection with HIV, Hepatitis B, or Hepatitis C
  • Female subjects who are pregnant or breast feeding
  • Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities
  • Clinically significant uncontrolled condition(s)
  • Subjects in Arm C who have advanced malignant hepatic tumors
  • Subjects in Arm C who have hypersensitivity to azacitidine or mannitol
  • Subjects have received CYP3A inhibitors or inducers within 7 days prior to the first dose of study drug.
  • Subjects enrolled in Arm D who have hypersensitivity to drugs formulated with polyethoxylated castor oil (Cremophor).

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Site Reference ID/Investigator# 26523

    Atlanta, Georgia, 30322

  • Site Reference ID/Investigator# 26522

    Houston, Texas, 77030-4009

  • Site Reference ID/Investigator# 59324

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-348 as Monotherapy and in Combination With Azacitidine in Subjects With Advanced Hematologic Malignancies

The purpose of this study is to determine the safety, pharmacokinetics and maximum tolerated dose of ABT-348 as monotherapy and when given in combination with azacitidine.

Read the detailed description

The primary objectives of this study are to determine safety and pharmacokinetics of ABT-348 as monotherapy and when given in combination with azacitidine. The secondary objectives are to determine the maximum tolerated dose and recommended Phase 2 dose of ABT-348 when administered as monotherapy and when given in combination with azacitidine in subjects with advanced hematologic malignancies.

Being tested
ABT-348, ABT-348 and azacitidine
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Anemia, Refractory, with Excess of Blasts

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABT-348Drug

    An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.

  • ABT-348Drug

    An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle

  • ABT-348 and azacitidineDrug

    An oral dose of ABT-348 on Day 1, Day 8, and Day 15 of each 28 day cycle. An IV or injection of azacitidine on Days 1-7 of each 28 day cycle.

  • ABT-348Drug

    An intravenous dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.

Study groups in NCT01110473
Study groupRoleWhat they receive
Monotherapy, once dailyExperimentalNot described
Receives: Drug: ABT-348
Monotherapy, twice dailyExperimentalNot described
Receives: Drug: ABT-348
Combination with AzacitidineExperimentalNot described
Receives: Drug: ABT-348; Drug: ABT-348 and azacitidine
IV monotherapy, once dailyExperimentalNot described
Receives: Drug: ABT-348

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine the safety profile (adverse events by toxicity grade and relationship to study drug, serious adverse events, adverse events leading to discontinuation and relevant clinical laboratory abnormalities) of ABT-348 as monotherapy or in combination

    Measured: At each treatment visit

  2. Study the pharmacokinetic interaction (plasma concentrations and pharmacokinetic parameter values) of ABT-348 as monotherapy and in combination

    Measured: At study visits

Secondary outcomes (1)

  1. Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) of ABT-348 when administered as a monotherapy and in combination in subjects with advanced hematologic malignancies

    Measured: At each treatment visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionJun 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01110473
Sponsor's protocol ID
M10-943
Status last verified
Nov 2013
First submitted
26 Mar 2010
Last updated
20 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Garcia-Manero G, Tibes R, Kadia T, Kantarjian H, Arellano M, Knight EA, Xiong H, Qin Q, Munasinghe W, Roberts-Rapp L, Ansell P, Albert DH, Oliver B, McKee MD, Ricker JL, Khoury HJ. Phase 1 dose escalation trial of ilorasertib, a dual Aurora/VEGF receptor kinase inhibitor, in patients with hematologic malignancies. Invest New Drugs. 2015 Aug;33(4):870-80. doi: 10.1007/s10637-015-0242-6. Epub 2015 May 2.

    PubMed 25933833

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABT-348 and ABT-348 and azacitidine in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by AbbVie (prior sponsor, Abbott) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the safety profile (adverse events by toxicity grade and relationship to study drug, serious adverse events, adverse events leading to discontinuation and relevant clinical laboratory abnormalities) of ABT-348 as monotherapy or in combination (time frame: At each treatment visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01110473, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2017.

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