The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00788684




Registration number
NCT00788684
Ethics application status
Date submitted
10/11/2008
Date registered
11/11/2008
Date last updated
20/02/2020

Titles & IDs
Public title
Safety Study of ABT-263 in Combination With Rituximab in Lymphoid Cancers
Scientific title
A Phase 1 Study Evaluating the Safety of ABT-263 in Combination With Rituximab in Subjects With CD20-positive Lymphoid Malignancies
Secondary ID [1] 0 0
M10-166
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CD20-Positive Lymphoid Malignancies 0 0
Chronic Lymphoid Leukemia 0 0
Hematological Malignancies 0 0
Non-Hodgkin's 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
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - rituximab
Treatment: Drugs - ABT-263

Experimental: ABT-263 + rituximab -


Treatment: Drugs: rituximab
IV infusion once weekly for four doses

Treatment: Drugs: ABT-263
ABT-263: oral solution or tablets, once daily dosing until disease progression

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

Outcomes
Primary outcome [1] 0 0
Extension Study: Continued assessment of the safety profile of ABT-263 when administered in combination with rituximab
Timepoint [1] 0 0
Safety will be assessed until the subject discontinues the extension portion of the study.
Primary outcome [2] 0 0
Assess the safety profile and characterize the pharmacokinetics of ABT-263 when administered in combination with rituximab
Timepoint [2] 0 0
Safety and pharmacokinetics will be assessed until the subject discontinues the study or transitions to the extension portion of the study (whichever comes first).
Primary outcome [3] 0 0
Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) when ABT-263 is administered in combination with rituximab
Timepoint [3] 0 0
DLTs and MTD will be assessed after all subjects in a dose level have completed the lead-in period plus 28 days if dosing with ABT-263 and rituximab
Secondary outcome [1] 0 0
Extension Study: Continued assessment of the preliminary progression-free survival (PFS), response rate, and duration of response.
Timepoint [1] 0 0
PFS will be measured upon study completion via statistical analysis of the study data.
Secondary outcome [2] 0 0
Preliminary progression-free survival (PFS), response rate, and duration of response.
Timepoint [2] 0 0
PFS will be measured upon study completion via statistical analysis of the study data.

Eligibility
Key inclusion criteria
- Diagnosed with a CD20-positive lymphoproliferative disorder (REAL/WHO) and
bi-dimensionally measurable disease with at least 1 lesion > or = 1.0 cm

- ECOG performance score of <or = 1

- Adequate bone marrow function, independent of growth factor support (with the
exception of subjects with bone marrow that is heavily infiltrated with underlying
disease [80% or more] who may use growth factor to achieve ANC eligibility criteria)
per local laboratory reference range as follows: Absolute Neutrophil count (ANC) =
1000/µL; Platelets = 100,000/mm3 (untransfused); Hemoglobin = 9.0 g/dL.

- Subjects who have a history of autologous stem cell transplant (e.g., bone marrow)
must be > 6 months post transplant and have adequate bone marrow function, independent
of any growth stimulating factors (with the exception of subjects with bone marrow
that is heavily infiltrated with underlying disease [80% or more] who may use growth
factor to achieve ANC eligibility criteria) per local laboratory reference range as
follows: Absolute Neutrophil count (ANC) = 1500/µL; Platelets = 125,000/mm3
(untransfused); Hemoglobin = 10.0 g/dL.

- Subject must have adequate renal, hepatic and coagulation function per local
laboratory reference range as follows: Serum creatinine = 2.0 mg/dL or calculated
creatinine clearance = 50 mL/min; AST and ALT = 3.0 × the upper normal limit (ULN);
Bilirubin = 1.5 × ULN. Subjects with Gilbert's Syndrome may have a Bilirubin > 1.5 ×
ULN; aPTT, PT not to exceed 1.2 × ULN

- Females must be surgically sterile, postmenopausal (at least 1 year), or have negative
pregnancy test at screening on serum sample and prior to first dose of study drug on
urine sample. Females not surgically sterile or postmenopausal (at least 1 year) and
non-vasectomized males must practice at least 1 of the following:total abstinence from
sexual intercourse (min.1 complete menstrual cycle),a vasectomized partner, hormonal
contraceptives for at least 3 months prior to study drug administration, or
double-barrier method.

Inclusion Criteria (Extension Study):

- Subjects who enter the Extension Study must continue to meet all Inclusion and
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria, with the exception of inclusion criteria regarding measurable
disease and inclusion criteria regarding laboratory parameters. Subjects entering the
Extension Study must also have stable lab values per local laboratory reference
ranges. In addition they must meet the following lab criteria:

- Subjects must meet the following hematology and coagulation lab criteria:

- Platelet counts must be = 25,000/mm3 (untransfused). Platelet counts = 50,000/mm3
must be stable and monitored at an increased frequency at the discretion of the
investigator.

- Absolute Neutrophil count (ANC) = 500/µL. ANC = 500/µL and < 1,000/µL should be
monitored at an increased frequency at the discretion of the investigator.

- Hemoglobin of = 8.0 g/dL.

- aPTT, PT is not to exceed 1.2 × ULN.

- Subjects' chemistry values must not exceed Grade 2. Grade 2 chemistry labs should be
monitored at an increased frequency at the discretion of the investigator. Subjects
must meet the following chemistry criteria:

- Serum creatinine = 3.0 × the upper normal limit (ULN) of institution's norma



- History of or clinically suspicious for cancer-related Central Nervous System (CNS)
disease, allogeneic stem cell transplant, recurrent significant infections, previous
or current malignancies within the last 5 years ( except: adequately treated in situ
carcinoma of the cervix uteri; basal or squamous cell carcinoma of the skin; in situ
carcinoma of the bladder; previous malignancy confined and surgically resected with
curative intent), toxicity from rituximab that resulted in permanent discontinuation
of treatment or toxicity from ABT-263 or another Bcl-2 family protein inhibitor,
significant cardiovascular disease (e.g., MI within 6 months), renal, neurologic,
psychiatric, endocrinologic, metabolic, immunologic or hepatic disease that would
adversely affect participation, severe (defined as Grade 4 and/or requiring permanent
discontinuation of prior antibody therapy) allergic or anaphylactic reactions to
human, humanized, chimeric or murine monoclonal antibodies

- The subject has an underlying, predisposing condition of bleeding or currently
exhibits signs of clinically significant bleeding. The subject has a recent history of
non-chemotherapy induced thrombocytopenic associated bleeding within six months prior
to the first dose of study drug. The subject has active peptic ulcer disease or other
hemorrhagic esophagitis/gastritis or active immune thrombocytopenic purpura (ITP) or a
history of being refractory to platelet transfusions (within six months prior to the
first dose of study drug).

- Female subject is pregnant or breast-feeding

- Subject has tested positive for HIV, Hepatitis B or Hepatitis C infection, (Subjects
who test positive for anti-HBc (carrier) will be allowed to enroll)

- Evidence of other clinically significant uncontrolled condition(s) including, but not
limited to: active systemic fungal infection; diagnosis of fever and neutropenia
within one week prior to study drug administration

- Received steroid therapy for anti-neoplastic intent within seven days prior to the
first dose of study drug,received aspirin within seven days prior to the first dose of
study drug, CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 7 days prior
to the administration of the first dose of study drug, radio-immunotherapy within six
months prior to first dose of study drug,received any anti-cancer therapy within
fourteen days prior to the first dose of study drug.

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 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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 Ctr /ID# 25067 - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital /ID# 9781 - Parkville
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Wisconsin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie (prior sponsor, Abbott)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1 study evaluating the safety of ABT-263 administered in combination with
rituximab in subjects with CD20-positive lymphoproliferative disorders. The extension portion
of the study will allow active subjects to continue to receive ABT-263 for up to 9 years
after the last subject transitions with quarterly study evaluations.
Trial website
https://clinicaltrials.gov/show/NCT00788684
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications