Brief Title
Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors
Official Title
A Phase 1b/2a Study of ABT-888 in Combination With Bendamustine +/- Rituximab in Lymphoma, Multiple Myeloma and Solid Tumors
Brief Summary
This phase I/II trial studies the side effects and the best dose of veliparib when given
together with bendamustine hydrochloride and rituximab and to see how well they work in
treating patients with lymphoma, multiple myeloma, or solid tumors that have come back or
have not responded to treatment. Veliparib may stop the growth of cancer cells by blocking
some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as bendamustine
hydrochloride, work in different ways to stop the growth of cancer cells, either by killing
the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can
block cancer growth in different ways. Some find cancer cells and help kill them or carry
cancer-killing substances to them. Others interfere with the ability of cancer cells to grow
and spread. Giving veliparib together with bendamustine hydrochloride and rituximab may kill
more cancer cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) of ABT-888 (veliparib) in combination with
bendamustine (bendamustine hydrochloride) in patients with solid tumors, lymphoma, or
multiple myeloma. (Phase Ib) II. To establish the safety of ABT-888 in combination with
bendamustine and rituximab in an expansion cohort of patients with non-Hodgkin lymphoma
(NHL). (Phase Ib) III. To assess the toxicity profile of this regimen in the above patients.
(Phase Ib) IV. To determine the complete response (CR) rate in patients with indolent NHL or
mantle cell lymphoma (MCL) treated with ABT-888 + bendamustine + rituximab. (Phase IIa)
SECONDARY OBJECTIVES:
I. To assess response rates and survival parameters of patients treated with ABT-888 +
bendamustine +/- rituximab. (Phase Ib) II. To assess pharmacokinetic parameters of ABT-888 in
this regimen. (Phase Ib) III. To assess progression-free survival, overall survival, and
duration of remission of patients with indolent NHL and MCL treated with ABT-888 +
bendamustine + rituximab. (Phase IIa)
OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.
Patients receive veliparib orally (PO) twice daily (BID) on days 1-7 and bendamustine
hydrochloride intravenously (IV) over 30-60 minutes on days 1-2. Treatment repeats every 28
days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Once the maximum-tolerated dose is determined, a cohort of patients receives veliparib and
bendamustine hydrochloride as above and rituximab IV on day 1. Treatment repeats every 28
days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum Tolerated Dose of Veliparib When Combined With Bendamustine Hydrochloride
Secondary Outcome
Complete Response (CR) to Study Treatment (Phase IIa)
Condition
Adult B Acute Lymphoblastic Leukemia
Intervention
Bendamustine Hydrochloride
Study Arms / Comparison Groups
Treatment (veliparib, bendamustine hydrochloride, rituximab)
Description: Patients receive veliparib PO BID on days 1-7 and bendamustine hydrochloride IV over 30-60 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Once the maximum-tolerated dose is determined, a cohort of patients receives veliparib and bendamustine hydrochloride as above and rituximab IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
43
Start Date
July 2011
Completion Date
April 2015
Primary Completion Date
April 2015
Eligibility Criteria
Inclusion Criteria:
- Phase 1b: Patients must have a histologically confirmed solid malignancy, lymphoma or
multiple myeloma for which standard curative or palliative measures do not exist, are
no longer effective, or for which the patient is not eligible or refuses; phase 1b
cohort expansion: patients must have a histologically confirmed cluster of
differentiation (CD)-20 positive B-cell non-Hodgkin lymphoma for which standard
curative or palliative measures do not exist, are no longer effective, or for which
the patient is not eligible or refuses; phase 2a: patients must have histologically or
cytologically confirmed marginal zone B-cell lymphoma, small lymphocytic lymphoma,
lymphoplasmacytic lymphoma or mantle cell lymphoma, and must have at least one
measureable site of disease
- For lymphoma and multiple myeloma patients: patients who have relapsed or are
refractory to at least one prior chemotherapeutic regimen or biologic agent; patients
must either be ineligible for or have refused curative options for treatment,
including stem cell transplant, if applicable
- For solid tumor patients: relapsed or refractory to at least one prior
chemotherapeutic regimen or biologic agent; patients must either be ineligible for or
have refused curative options for treatment
- Patients must have had a rest period of at least 3 weeks since prior chemotherapy or
radiation therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin
C; there must be a rest period of at least 3 months if the last therapy was
immunotherapy or radioimmunotherapy (unless the disease has progressed since
treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 3 months
- Absolute neutrophil count (ANC) >= 1,000/mcL
- Platelets >= 100,000/mcL unsupported by transfusion within the prior 2 weeks
- Hemoglobin >= 8.0 g/dL unsupported by transfusion within the prior 2 weeks
- Total bilirubin =< 2 x upper normal institutional limits; in patients with Gilbert's
disease or documented liver metastases, total bilirubin up to 3 x upper limits of
normal (ULN) will be allowed
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min for
patients with creatinine levels above institutional normal
- Patients with prior stem cell transplant will be eligible as long as they have not
relapsed or progressed within 100 days post-transplant and they meet the above
inclusion criteria
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal, barrier method of birth control, or abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect she
is pregnant while participating in this study, she should inform her treating
physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Toxicities from prior therapies must have resolved to baseline, or be =< grade 2 and
stable for at least one month
- Patient must be able to swallow pills
- Patients with central nervous system (CNS) metastases must be stable after therapy for
> 3 months and off steroid treatment prior to study enrollment
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered to baseline (or are not at stable grade =< 2) from adverse events due to
agents administered more than 3 weeks earlier; patients who have received
immunotherapy or radioimmunotherapy within 3 months, unless disease has progressed
since treatment; patients who have been administered ABT-888 as part of a single or
limited dosing study, such as a phase 0 study, will not be excluded from participating
in this study solely because of receiving prior ABT-888
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ABT-888, bendamustine or mannitol; patients enrolling in the cohort
expansion or phase 2 portions of the study who have been intolerant of repeated doses
of rituximab in the past will be excluded (patients who have had infusion reactions to
their initial dose of rituximab will not be excluded)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with ABT-888
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are eligible if their HIV is under adequate control with an antiretroviral
regimen that has been stable for >= 4 weeks, as long as the CD4 count is > 300;
appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated; patients on zidovudine or stavudine would not
be eligible
- Patients with active seizure or a history of seizure are not eligible
- Patients with uncontrolled CNS metastasis are not eligible
- Patients with unrelated prior malignancies must have undergone potentially curative
therapy for their prior malignancy, have no evidence of that disease for three years,
or be deemed at low risk for recurrence of their prior malignancy by her/his treating
physician; patients with dermal squamous cell carcinoma, basal cell carcinoma or
melanoma in situ that has been completely excised will be eligible following excision
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Gerecitano, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01326702
Organization ID
NCI-2011-02583
Secondary IDs
NCI-2011-02583
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
John Gerecitano, Principal Investigator, Memorial Sloan Kettering Cancer Center
Verification Date
November 2019