Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors
A Phase 1b/2a Study of ABT-888 in Combination With Bendamustine +/- Rituximab in Lymphoma, Multiple Myeloma and Solid Tumors
6 other identifiers
interventional
43
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2011
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 30, 2011
CompletedFirst Posted
Study publicly available on registry
March 31, 2011
CompletedStudy Start
First participant enrolled
July 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2015
CompletedResults Posted
Study results publicly available
December 16, 2019
CompletedDecember 16, 2019
November 1, 2019
3.8 years
March 30, 2011
September 18, 2018
November 22, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose of Veliparib When Combined With Bendamustine Hydrochloride
Maximum Tolerated Dose (MTD) reflects the highest dose of Veliparib when combined with Bendamustine Hydrochloride that did not cause a DLT. The maximum tolerated dose (MTD) was defined as the highest dose level at which 33% of patients experienced DLT.
28 days
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
2 years
Number of Participants With Adverse Events
Adverse events assessed by NCI CTCAE version 4.0 (Phase Ib) See adverse events section.
2 years
Secondary Outcomes (6)
Complete Response (CR) to Study Treatment (Phase IIa)
2 years
Duration of Remission (Phase IIa)
From the first documented response to the first documented progression or death, assessed up to 30 days post-treatment
Overall Survival (Phase IIa)
Up to 30 days post-treatment
Pharmacokinetic Parameters of Veliparib (Phase Ib)
From time zero to 12 hours on day 2 of course 1
Progression-free Survival Using RECIST Version 1.1 (Phase IIa)
2 years
- +1 more secondary outcomes
Study Arms (1)
Treatment (veliparib, bendamustine hydrochloride, rituximab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Correlative studies
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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
- 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
- +2 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Related Publications (1)
Soumerai JD, Zelenetz AD, Moskowitz CH, Palomba ML, Hamlin PA Jr, Noy A, Straus DJ, Moskowitz AJ, Younes A, Matasar MJ, Horwitz SM, Portlock CS, Konner JA, Gounder MM, Hyman DM, Voss MH, Fury MG, Gajria D, Carvajal RD, Ho AL, Beumer JH, Kiesel B, Zhang Z, Chen A, Little RF, Jarjies C, Dang TO, France F, Mishra N, Gerecitano JF. The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4119-4126. doi: 10.1158/1078-0432.CCR-16-3068. Epub 2017 Mar 17.
PMID: 28314788DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. John Gerecitano
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
John Gerecitano
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 30, 2011
First Posted
March 31, 2011
Study Start
July 1, 2011
Primary Completion
April 1, 2015
Study Completion
April 1, 2015
Last Updated
December 16, 2019
Results First Posted
December 16, 2019
Record last verified: 2019-11