IIT CTI Bendamustine, Rituximab, Pixantrone in Relapsed/Refractory B Cell Non-Hodgkin's Lymphoma (BRP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Duke University
Sponsor:
Collaborator:
CTI BioPharma
Information provided by (Responsible Party):
Anne Beaven, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01491841
First received: November 14, 2011
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

Part 1: This is a phase I trial of the combination of bendamustine, rituximab and pixantrone in patients with relapsed/refractory B cell non-Hodgkin lymphoma. A standard 3+3 design will be used to determine the maximum tolerated dose (MTD) of the combination. A static dose of bendamustine and rituximab will be used and the dose of pixantrone will be escalated in each cohort. Pixantrone will be dosed on a 21 day cycle at 55mg/m2, 85mg/m2, and 115mg/m2 in sequential cohorts dependent on acceptable toxicity profile at each dose level. MTD will be determined based on DLTs that occur during the first 2 cycles of the drug combination.

After 2 cycles of study drug, all subjects achieving stable disease or better may continue on study for up to 6 cycles. However, adverse events occurring during cycles 3-6 will not be considered DLTs and will not contribute to the determination of the MTD.

Part 2: After the MTD is determined an expansion study is planned. This will be a phase II, prospective, open label, single arm study of combination therapy with bendamustine, rituximab, and pixantrone at the defined MTD schedule based on the phase I portion of this study. Subjects enrolled in part 2 of the study must have an aggressive, relapsed or refractory B-cell NHL, to include follicular lymphoma (FL) grade 3, Diffuse Large B Cell Lymphoma (DLBCL), transformed NHL, mantle cell lymphoma (MCL), and other aggressive histologies. We anticipate the total sample size to be 36 patients accrued at a rate of 2 patients per month. Restaging will be employed after cycle 2, and if the patient has stable disease or better they may continue on study for up to 6 cycles.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Bendamustine + Rituximab + Pixantrone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of the Combination of Bendamustine, Rituximab and Pixantrone in Patients With Relapsed/Refractory B Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Response [ Time Frame: From day 1 of treatment to best response from study drugs ] [ Designated as safety issue: No ]
    Partial response and complete response

  • Progression free survival [ Time Frame: From day 1 of treatment to disease progression, death or 5 years, whichever comes first ] [ Designated as safety issue: No ]
  • Toxicity (number of participants with adverse events) [ Time Frame: 30 days post last dose of study drug ] [ Designated as safety issue: Yes ]
    Particular attention will be paid to dose limiting toxicities and to changes in the left ventricular ejection fraction

  • Overall survival [ Time Frame: from day 1 of treatment to death ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: November 2011
Estimated Study Completion Date: November 2021
Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine + Rituximab + Pixantrone Drug: Bendamustine + Rituximab + Pixantrone
Maximum tolerated dose and optimal dose schedule of pixantrone in combination with static dose bendamustine (120mg/m2 on d1 of 21 day) and rituximab (375mg/m2 on d1 of 21 day cycle).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Part I: Subjects must have relapsed or refractory B cell NHL;
  2. Part II: Subjects must have relapsed or refractory aggressive B cell NHL including follicular lymphoma (FL) grade 3, Diffuse Large B Cell Lymphoma (DLBCL), transformed NHL, mantle cell lymphoma (MCL), or other aggressive B cell NHL histology as per the WHO 2008 criteria;
  3. Refractory disease (defined as persistence of evaluable disease after therapy) or relapsed disease following at least one prior treatment regimen that should include autologous stem cell transplant unless a patient was not eligible or refused prior transplant;
  4. Age ≥ 18 years old;
  5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2;
  6. Subjects must have measurable or evaluable disease based on physical exam and/or radiographs (CT, MRI, PET) or bone marrow involvement;
  7. Female subject is either post-menopausal or surgically sterilized;
  8. Laboratory Values:

    • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L; lower levels accepted if due to marrow involvement by lymphoma
    • Platelets ≥ 75,000/mcl; lower levels accepted if due to marrow involvement by lymphoma
    • Total bilirubin ≤ 1.5 X institutional upper limit of normal; ≤ 3.0 ULN accepted in subjects with Gilbert's Syndrome
    • AST/ALT ≤ 1.5 X institutional upper limit of normal. Subjects with known liver involvement by lymphoma: AST/ALT ≤ 2 X institutional upper limit of normal
    • Serum creatinine < 1.5 X institutional upper limit of normal
  9. Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

Exclusion Criteria:

  1. No chemotherapy, radiation, biologics or immunotherapy within 2 weeks prior to registration (6 weeks if last received BCNU or mitomycin C).
  2. No radioimmunotherapy within 2 months prior to registration.
  3. Subjects receiving chronic, systemic treatment with corticosteroids equivalent to > 20mg of prednisone per day. Subjects receiving replacement for adrenal insufficiency will be allowed on the study. Topical or inhaled corticosteroids are allowed.
  4. Subjects with a history of another primary malignancy ≤ 3 years ago, with the exception of inactive basal, squamous cell carcinoma of the skin or superficial melanoma only requiring excision, prostate cancer with a PSA that has not increased for at least 3 months, carcinoma in situ of the cervix.
  5. Major surgery ≤ 4 weeks prior to registration. Minor surgery ≤ 2 weeks prior to registration. Insertion of a vascular access device is not considered major or minor surgery. Subjects must have recovered from all surgery related toxicities to ≤ grade 1 or to baseline if subject started with > grade 1 toxicity, not otherwise violating the above inclusion criteria.
  6. Subjects who have received investigational drugs ≤ 4 weeks prior to registration.
  7. Impaired Cardiac Function:

    • QTc > 480 on screening ECG.
    • Previous history of angina pectoris or acute MI within 6 months
    • Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/ECHO shows LVEF < 45%
    • Any history of torsade de pointes, ventricular fibrillation, uncontrolled ventricular tachycardia, or uncontrolled atrial fibrillation.
  8. Female patients who are pregnant or breastfeeding
  9. Patients with history of untreated hepatitis B or who are known carriers of hepatitis B will be excluded from this trial. All subjects will be screened prior to study entry.
  10. Concurrent use of other anti-cancer agents or anti-cancer treatments.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491841

Contacts
Contact: Annie Tsui, RN, MSN (919) 681-4769 annie.tsui@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Principal Investigator: Anne Beaven, MD         
Sponsors and Collaborators
Anne Beaven, MD
CTI BioPharma
Investigators
Principal Investigator: Anne Beaven, MD Duke University
  More Information

No publications provided

Responsible Party: Anne Beaven, MD, Assist Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01491841     History of Changes
Other Study ID Numbers: Pro00030834
Study First Received: November 14, 2011
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bendamustine
Nitrogen Mustard Compounds
Pixantrone
Rituximab
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014