Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)

NCT01439750 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: PSHCI 10-011
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I/II trial of bortezomib, cladribine, and rituximab in newly diagnosed and relapsed mantle cell lymphoma (MCL). The phase I component has three dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2) and is designed as a traditional dose-escalation study in which cohorts of 3 patients are evaluated for the incidence of dose-liming toxicity (DLT) at each dose level. Once the maximum tolerated dose (MTD) is determined, a phase II component with 2 arms will begin. One arm will enroll newly diagnosed MCL patients and one arm will enroll relapsed MCL patients. Each arm is a single-stage, fixed sample size study and will be accrued and analyzed separately. The phase I and II data will also be analyzed separately.

Conditions

Mantle Cell Lymphoma

Keywords

mantle cell lymphoma; lymphoma

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Dose Limiting Tolerability

  Dose Limiting Tolerability as measured by CTCAEv.4 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .

  2 years

Secondary Outcomes (1)

• Secondary Outcome objective response rates

  7 months

Study Arms (2)

Phase I

EXPERIMENTAL

The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of cladribine in the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Rituximab 375 mg/m2 on day 5,12, 19, 26 for 1st cycle, then day 5 of cladribine for next 5 cycles and then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days 1-5 for 6 cycles. Bortezomib 1.6 mg/m2 sub Q days 12,19,26 for 3 cycle, then every 2 weeks maintenance dose until toxicity or progression.

Drug: Rituximab; Drug: bortezomib; Drug: Cladribine

Phase II

EXPERIMENTAL

The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms. Rituximab 375 mg/m2 on day 5,12,19,26 for 1st cycles, then day 5 montly for next 5 cycles, then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days for 6 cycles (dose determined from phase I). Bortezomib 1.6 mg/m2 weekly on day 12,19,26 for 3 cycles then every 2 weeks as maintenance dose until toxicity or progression.

Drug: Rituximab; Drug: bortezomib; Drug: Cladribine

Interventions

Rituximab DRUG

375 mg/m2 on day 5, 12, 19, 26 of Cycle1; and day 5 of Cycles 2-6; then every 2 months as maintenenace dose

Also known as: Rituxam

Phase I; Phase II

bortezomib DRUG

1.6 mg/m2 day 12, 19, 26 for 3 cycles (28 days). Then beginning with Cycle 4, 1.6/mg/m2 every two weeks (Days 5 and 19; maintenance every other week until toxicity or proression of disease).

Also known as: VELCADE

Phase I; Phase II

Cladribine DRUG

Phase I will use 3 dose levels Level 1: caldribine (2-CdA) 3mg/m2 days 1-5; Level 2 caldribine 4mg/m2 days 1-5; Level 3: cladribine 5mg/m2 days 1-5

Also known as: Litak, Movectro

Phase I; Phase II

Eligibility Criteria

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

You may qualify if:

• Females that are postmenopausal for at least 1 year before the screening visit, surgically sterilized or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose.
• Male subjects must agree to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
• Patients with newly diagnosed and relapsed mantle cell lymphoma.
• ECOG performance status grade 3 or higher.

You may not qualify if:

• Patient has a platelet count of \<50x10 9/L within 14 days before enrollment if not related to disease.
• Patient has an absolute neutrophil count less than 100 within 14 days before enrollment if not related to disease.
• Patient has a calculated or measured creatinine clearance of \<20 mL/minute within 14 days before enrollment.
• Patient has \> Grade 2 peripheral neuropathy within 14 days before enrollment.
• Patient has \> 1.5 x ULN total bilirubin.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class II or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding.
• Patient has received other investigational drugs within 14 days before enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (2)

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (1)

• Pu JJ, Berger KN, Zheng C, Do N, Claxton DF, Ehmann WC, Drabick JJ, Li H, Loughran TP Jr, Epner EM. A phase I study using bortezomib (Velcade), cladribine, and rituximab in treating patients over 50 years old with mantle cell lymphoma. Front Oncol. 2024 Dec 16;14:1449401. doi: 10.3389/fonc.2024.1449401. eCollection 2024.

  PMID: 39737396 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma

Interventions

Rituximab; Bortezomib; Cladribine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jeffrey J Pu, MD PhD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 16, 2011
• First Posted: September 23, 2011
• Study Start: May 1, 2012
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2020
• Last Updated: August 7, 2017

Record last verified: 2017-08

Locations

US (2)