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

NCT01491841 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro00030834
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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. Phase II did not proceed as planned due to withdrawal of pixantrone from the US.

Conditions

Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Dose-limiting toxicity (DLT) assessments were performed weekly during cycles 1 and 2. A DLT was defined as any grade 3 non-hematologic toxicity that lasted longer than 48 hours, despite proper supportive care, any grade 4 non-hematologic toxicity, or any grade 3 or 4 hematologic toxicity lasting longer than 7 days. Alopecia and febrile neutropenia were not considered DLTs. Any NCI CTC (National Cancer Institute Common Terminology Criteria) v4.03 grade 5 (death) toxicity was considered a DLT. Dose Limiting Toxicities were used as the assessment criteria to determine the Maximum Tolerated Dose (MTD). MTD is presented.

  4 years

Secondary Outcomes (4)

• Overall Response

  up to 220 days

• Progression Free Survival

  From day 1 of treatment to disease progression, death or 5 years, whichever comes first

• Toxicity

  30 days post last dose of study drug

• Overall Survival

  from day 1 of treatment to death

Study Arms (3)

Phase 1: Pixantrone, 55mg/m^2

EXPERIMENTAL

Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 55mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle

Drug: Bendamustine + Rituximab + Pixantrone; Drug: Pegfilgrastim

Phase 1: Pixantrone, 85mg/m^2

EXPERIMENTAL

Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 85mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle

Drug: Bendamustine + Rituximab + Pixantrone; Drug: Pegfilgrastim

Phase 1: Pixantrone, 115mg/m^2

EXPERIMENTAL

Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 115mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle

Drug: Bendamustine + Rituximab + Pixantrone; Drug: Pegfilgrastim

Interventions

Bendamustine + Rituximab + Pixantrone DRUG

Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle).

Also known as: BRP; BuRP

Phase 1: Pixantrone, 115mg/m^2; Phase 1: Pixantrone, 55mg/m^2; Phase 1: Pixantrone, 85mg/m^2

Pegfilgrastim DRUG

6mg administered on Day 2 of each 21 day cycle

Phase 1: Pixantrone, 115mg/m^2; Phase 1: Pixantrone, 55mg/m^2; Phase 1: Pixantrone, 85mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part I: Subjects must have relapsed or refractory B cell NHL;
• 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;
• 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;
• Age ≥ 18 years old;
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2;
• Subjects must have measurable or evaluable disease based on physical exam and/or radiographs (CT, MRI, PET) or bone marrow involvement;
• Female subject is either post-menopausal or surgically sterilized;
• Laboratory Values:
• Absolute neutrophil count (ANC) ≥ 1.5 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
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

You may not qualify if:

• No chemotherapy, radiation, biologics or immunotherapy within 2 weeks prior to registration (6 weeks if last received BCNU or mitomycin C).
• No radioimmunotherapy within 2 months prior to registration.
• 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.
• 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.
• Subjects who have received investigational drugs ≤ 4 weeks prior to registration.
• 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 estimated LVEF \< 45%
• Any history of torsade de pointes, ventricular fibrillation, uncontrolled ventricular tachycardia, or uncontrolled atrial fibrillation.
• Female patients who are pregnant or breastfeeding
• 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.
• Concurrent use of other anti-cancer agents or anti-cancer treatments.

Sponsors & Collaborators

• Anne Beaven, MD: lead
• CTI BioPharma: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Bendamustine Hydrochloride; Rituximab; pixantrone; pegfilgrastim

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: David Rizzieri, MD
• Organization: Duke University Medical Center

david.rizzieri@duke.edu

919-668-1040

Study Officials

• David Rizzieri, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assist Professor of Medicine

Model Details: Dose Escalation, 3+3 design

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: December 14, 2011
• Study Start: November 1, 2011
• Primary Completion: November 22, 2016
• Study Completion: February 17, 2017
• Last Updated: March 4, 2020
• Results First Posted: June 14, 2019

Record last verified: 2020-03

Locations

US (1)