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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02471391




Registration number
NCT02471391
Ethics application status
Date submitted
12/05/2015
Date registered
15/06/2015
Date last updated
31/08/2015

Titles & IDs
Public title
ABT-199 & Ibrutinib in Mantle Cell Lymphoma (AIM)
Scientific title
A Phase 2 Study of ABT-199 in Combination With Ibrutinib in the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma (AIM Study)
Secondary ID [1] 0 0
14/148
Universal Trial Number (UTN)
Trial acronym
AIM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mantle Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABT-199
Treatment: Drugs - Ibrutinib

Experimental: Ibrutinib + ABT-199 -


Treatment: Drugs: ABT-199


Treatment: Drugs: Ibrutinib


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete response measured using IWG at 16 weeks
Timepoint [1] 0 0
Measured at 16 weeks after commencement of treatment.
Secondary outcome [1] 0 0
Completing 4, 16, 28, 40 and 56 weeks of treatment
Timepoint [1] 0 0
Assessed at 4, 16, 28, 40 and 56 weeks
Secondary outcome [2] 0 0
Toxicities measured using CTCAE version 4
Timepoint [2] 0 0
Continuously measured while on treatment up to a maximum of 56 weeks
Secondary outcome [3] 0 0
Overall response (CR + PR) using IWG criteria at 4, 16, 28, 40 and 56 weeks
Timepoint [3] 0 0
Assessed at 4, 16, 28, 40 and 56 weeks
Secondary outcome [4] 0 0
Complete response using IWG criteria at 4, 16, 28, 40 and 56 weeks
Timepoint [4] 0 0
Assessed at 4, 16, 28, 40 and 56 weeks
Secondary outcome [5] 0 0
Minimal residual disease (MRD) at 4, 16, 28, 40 and 56 weeks
Timepoint [5] 0 0
Assessed at 4, 16, 28, 40 and 56 weeks
Secondary outcome [6] 0 0
Progression free survival
Timepoint [6] 0 0
From start of treatment until the date of first documented progression or date of death from any cause, whichever occures first, assessed up to the date when the last patient has their 13 months assessment.
Secondary outcome [7] 0 0
Overall survival
Timepoint [7] 0 0
From start of treatment until the date of death from any cause assessed up to the date when the last patient has their 13 months assessment.
Secondary outcome [8] 0 0
Duration of response
Timepoint [8] 0 0
From first disease response date to the date of earliest recurrance or PD, assessed up to the date when the last patient has their 13 months assessment.
Secondary outcome [9] 0 0
Time to progression
Timepoint [9] 0 0
From start of treatment until the date of first documented progression assessed up to the date when the last patient has their 13 months assessment.

Eligibility
Key inclusion criteria
1. Subject must be >/= 18 years of age.

2. Subject must have a confirmed diagnosis of Mantle Cell Lymphoma (MCL) according to WHO
(2008) criteria, and have received at least one prior line of systemic therapy for
MCL.

3. Subject requires treatment in the opinion of the investigator, and has at least one
site of radiographically assessable disease not previously irradiated (lymph node with
largest diameter >/= 1.5cm, or unequivocal hepatomegaly / splenomegaly)

4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of </= 2.

5. Subject must have adequate bone marrow function at Screening as follows:

- Absolute Neutrophil Count (ANC) >/= 1.0 x 109/L (neutropenia due to marrow
infiltration may be supported by growth factors);

- Platelets >/= 50 x 109/L (entry platelet count must be independent of transfusion
within 7 days).

6. Subject must have adequate coagulation, renal, and hepatic function, per laboratory
reference range at Screening as follows:

- aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN);

- Serum creatinine not to exceed 2 x ULN, and a calculated creatinine clearance of
at least 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine
collection;

- AST or ALT </= 3.0 × the upper normal limit (ULN) of institution's normal range;
Bilirubin </= 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have a
bilirubin > 1.5 × ULN.

7. Female subjects of childbearing potential and non-sterile male subjects (with partners
of child bearing potential) must practice at least one of the following methods of
birth control with partner(s) from initial study drug administration to 90 days after
the last dose of study drug:

- Total abstinence from sexual intercourse as the preferred life style of the
subject; periodic abstinence is not acceptable;

- Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy,
bilateral tubal ligation, bilateral oophorectomy or hysterectomy;

- Intrauterine device (IUD);

- Double-barrier method (contraceptive sponge, diaphragm or cervical cap with
spermicidal jellies or cream AND a condom);

- Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months
prior to study drug administration.

8. Female subjects of childbearing potential must have a negative serum (beta-human
chorionic gonadotropin [B-hCG]) or urine pregnancy test at Screening. Women who are
pregnant or breastfeeding are ineligible for this study

9. Male subjects must agree to refrain from sperm donation, from initial study drug
administration until 90 days after the last dose of study drug.

10. Subject is able to swallow whole tablets.

11. Subject (or their legally-acceptable representatives) must sign an informed consent
document indicating that they understand the purpose of and procedures required for
the study, including biomarkers, and are willing to participate in the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has undergone an allogeneic stem cell transplant within the last 6 months or
currently has active graft-vs-host disease requiring the use of immunosuppressants.

2. Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including
autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP).

3. Subject has known central nervous system involvement by MCL.

4. Subject previously participated in an ibrutinib clinical trial or subject previously
received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib

5. Subject has received the following within 30 days prior to the first dose of study
drug:

•Monoclonal antibody given with anti-neoplastic intent.

6. Subject has received any of the following within 14 days prior to the first dose of
study drug, or has not recovered to less than CTC grade 2 clinically significant
adverse effect(s)/toxicity(s) of the previous therapy:

- Any anti-cancer therapy including chemotherapy, or radiotherapy;

- Investigational therapy, including targeted small molecule agents.

7. Subject has received the following within 7 days prior to the first dose of study
drug:

•Steroid therapy given with anti-neoplastic intent

8. Subjects requires ongoing therapy with:

- Potent CYP3A inhibitors (such as indinavir, ketoconazole, and clarithromycin),

- Potent CYP3A inducers (e.g., rifampin, phenytoin, carbamazepine or St. John's
Wort),

- Warfarin, or or equivalent vitamin K antagonist (eg, phenprocoumon),

- Antiretroviral medications.

9. Subject has consumed the following within 3 days prior to the first dose of study
drug.

- Grapefruit, or

- Grapefruit products, or

- Seville oranges (including marmalade containing Seville oranges), or

- Star fruit

10. Subject has clinically significant cardiovascular disease such as uncontrolled or
symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6
months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as
defined by the New York Heart Association Functional Classification.

11. Subject has a life-threatening illness, medical condition, or organ system dysfunction
which, in the investigator's opinion, could compromise the subject's safety, interfere
with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at
undue risk.

•specifically, a subject with history of stroke or intracranial hemorrhage within 6
months prior to enrollment is excluded

12. Subject has a history of other active malignancies other than MCL within the past 2
years prior to study entry, with the exception of:

- Adequately treated in situ carcinoma of the cervix uteri,

- Adequately treated basal cell carcinoma of the skin or localized squamous cell
carcinoma of the skin,

- Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent.

13. Subject has known history of human immunodeficiency virus (HIV) or active Hepatitis C
Virus or active Hepatitis B Virus infection or any uncontrolled active systemic
infection requiring intravenous (IV) antibiotics.

14. Received live, attenuated vaccines within 4 weeks of first dose of ibrutinib

15. Major surgery within 4 weeks of first dose of ibrutinib

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This research will test the combination of two new drugs, called ibrutinib and ABT199, taken
together in the treatment of Mantle Cell Lymphoma. Other studies have indicated the potential
for these drugs to be used in the treatment of participants with Mantle Cell Lymphoma. In
this study, the investigators will test the combination of the two drugs together, in order
to determine what effects (good and bad) it has on mantle cell lymphoma.

This study has two phases. The first phase is the Primary Evaluation Phase and will closely
monitor the effects of ibrutinib and ABT199 for a period of 13 months. Participants who
complete 13 months of treatment and continue benefiting from the study treatments will be
allowed to continue both drugs until progression or intolerance in the Continuation Phase.
The purpose of this phase is to provide patients with continuing access to both ibrutinib and
ABT199. Patients will receive routine care from clinician, who will record any sideeffects
that may be experienced.

This is one of the first trials in the world to study the combination of ibrutinib and ABT199
together. Therefore the effectiveness of the combination of the study drugs will be assessed,
as will how they affect mantle cell lymphoma and how it develops resistance to the
treatments. The investigators also do not know whether combining the two drugs together will
cause unexpected side effects. Therefore, the study will monitor patients closely and perform
scans, blood tests, bone marrow biopsies and other tests at regular intervals.
Trial website
https://clinicaltrials.gov/show/NCT02471391
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Constantine Tam, MBBS (Hons), MD, FRACP, FRCPA
Address 0 0
Country 0 0
Phone 0 0
+61 3 9656 1700
Fax 0 0
Email 0 0
constantine.tam@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02471391