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Adult B Acute Lymphoblastic LeukemiaPhase 1/2NCT01326702

Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors

A Phase 1/2 study testing Bendamustine Hydrochloride, Pharmacological Study and Rituximab in people with Adult B Acute Lymphoblastic Leukemia and Adult Nasal Type Extranodal NK/T-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bendamustine Hydrochloride, Pharmacological Study and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
Jul 2011to Apr 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 1b/2a Study of ABT-888 in Combination With Bendamustine +/- Rituximab in Lymphoma, Multiple Myeloma and Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Bendamustine Hydrochloride, Pharmacological Study, Rituximab, Veliparib
Medical subject headings
Burkitt Lymphoma, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Intraocular Lymphoma, Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bendamustine HydrochlorideDrug

    Also called Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin

    Given IV

  • Pharmacological StudyOther

    Correlative studies

  • RituximabBiological

    Also called BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102

    Given IV

  • VeliparibDrug

    Also called ABT-888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT01326702
Study groupRoleWhat they receive
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.
Receives: Drug: Bendamustine Hydrochloride; Other: Pharmacological Study; Biological: Rituximab; Drug: Veliparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days

  2. 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.

    Measured: 2 years

  3. Number of Participants With Adverse Events

    Adverse events assessed by NCI CTCAE version 4.0 (Phase Ib) See adverse events section.

    Measured: 2 years

Secondary outcomes (6)

  1. Complete Response (CR) to Study Treatment (Phase IIa)

    Summary statistics will be used for CR. Responses will be evaluated by the International Uniform Response Criteria for Multiple Myeloma.

    Measured: 2 years

  2. Duration of Remission (Phase IIa)

    Measured: From the first documented response to the first documented progression or death, assessed up to 30 days post-treatment

  3. Overall Survival (Phase IIa)

    Kaplan-Meier estimates will be calculated and log-rank tests will be employed when certain comparisons are needed.

    Measured: Up to 30 days post-treatment

  4. Pharmacokinetic Parameters of Veliparib (Phase Ib)

    Area Under the Curve from time zero to 12 hours following Veliparib administration

    Measured: From time zero to 12 hours on day 2 of course 1

  5. Progression-free Survival Using RECIST Version 1.1 (Phase IIa)

    Kaplan-Meier estimates will be calculated and log-rank tests will be employed when certain comparisons are needed. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

    Measured: 2 years

  6. Participants With Dose Limiting Toxicities

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionApr 2015
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01326702
Sponsor's protocol ID
NCI-2011-02583
Other IDs
NCI-2011-02583, CDR0000697580, 10-174, 8818, P30CA008748, U01CA069856
Status last verified
Nov 2019
First submitted
30 Mar 2011
Last updated
16 Dec 2019

Publications

  • 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.

    PubMed 28314788

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bendamustine Hydrochloride, Pharmacological Study and Rituximab in people with Adult B Acute Lymphoblastic Leukemia and Adult Nasal Type Extranodal NK/T-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose of Veliparib When Combined With Bendamustine Hydrochloride (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01326702, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.

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