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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00788684




Registration number
NCT00788684
Ethics application status
Date submitted
10/11/2008
Date registered
11/11/2008
Date last updated
18/05/2023

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 participant 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 participant 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 participants 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 (Revised European American
Lymphoma [REAL]/World Health Organization [WHO]) and bi-dimensionally measurable
disease with at least 1 lesion >= 1.0 cm

- Eastern Cooperative Oncology Group (ECOG) performance score of <= 1

- Adequate bone marrow function, independent of growth factor support (with the
exception of participants with bone marrow that is heavily infiltrated with underlying
disease [80% or more] who may use growth factor to achieve Absolute Neutrophil count
(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.

- Participants 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 participants 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.

- Participant 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. Participants with Gilbert's Syndrome may have a Bilirubin >
1.5 × ULN; activated partial thromboplastin time (aPTT), prothrombin time (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 obtained within 14 days prior to initial
study drug administration, and prior to dosing on a urine obtained on Lead-in Day 1,
if it has been > 7 days since obtaining the serum pregnancy test results. 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
(minimum 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) Participants who enter the Extension Study must
continue to meet all Inclusion and
Minimum age
18 Years
Maximum age
No limit
Sex
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. Participants entering the Extension Study must also have stable lab values per
local laboratory reference ranges. In addition they must meet the following lab criteria:

- Participants 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.

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

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

- AST and ALT <= 5.0 × the upper normal limit (ULN) of institution's normal range.

- Bilirubin <= 3 × ULN. Participants with Gilbert's Syndrome may be allowed to have
a Bilirubin > 3 × ULN based on a joint decision between the investigator and
AbbVie medical monitor.



- 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 participant has an underlying, predisposing condition of bleeding or currently
exhibits signs of clinically significant bleeding. The participanthas a recent history
of non-chemotherapy induced thrombocytopenic associated bleeding within six months
prior to the first dose of study drug. The participant 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 participant is pregnant or breast-feeding

- Participant has tested positive for HIV, Hepatitis B or Hepatitis C infection,
(Participants 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
21/07/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/05/2024
Actual
Sample size
Target
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Ctr /ID# 25067 - Melbourne
Recruitment hospital [2] 0 0
The 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
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 participants with CD20-positive lymphoproliferative disorders. The extension
portion of the study will allow active participants to continue to receive ABT-263 for up to
13 years after the last participant transitions with quarterly study evaluations.
Trial website
https://clinicaltrials.gov/ct2/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