Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

Lymphoma, Mantle-Cell Clinical Trial

Official title:

Multi-institution Phase I/Ib Study of Ibrutinib With ABT-199 in Relapsed/Refractory Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02419560
• Other study ID #: 17983
• Secondary ID: ABT199-MCL-UVA-0
• Status: Completed
• Phase: Phase 1
• Start date: April 2015
• Est. completion date: May 2021

Study information

• Verified date: May 2022
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL).

Description:

This is a multi-center, study which will be open at up to 4 clinical sites. The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The main criterion for eligibility is MCL with measurable disease which is relapsed or refractory to at least 1 chemotherapy-containing regimen and has not been previously treated with ibrutinib.

This dose finding study will use a continual reassessment method, which accounts for both toxicity and efficacy in combinations of agents, to determine the optimal combination of the approved treatment ibrutinib with the investigational agent ABT-199. This study will accrue patients in two stages. In the initial stage, subjects will be accrued to dosing cohorts of increasing dosages of ABT-199 in combination with ibrutinib. The modeling is initiated once 1 subject experiences a dose limiting toxicity (DLT). During the modeling stage, treatment assignments will be made based on model prediction.

Subjects will remain on treatment until progression or unacceptable toxicity, and will be monitored for safety during the treatment interval. Safety will be evaluated by incidence of adverse events and number of discontinuations due to AEs. Efficacy endpoints include Overall Response Rate (ORR), Complete Response Rate (CRR), minimal residual disease response rate, and survival (PFS and OS). The study will also include exploratory analysis of the gene expression pattern in subjects who progress on treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosed with Mantle Cell Lymphoma and has had at least one chemotherapy.

2. Subjects must have measurable or evaluable disease.

3. ECOG Performance Status of 0-2.

4. Must be referred for treatment with ibrutinib.

5. Must have adequate organ function.

Exclusion Criteria:

1. Subject is pregnant.

2. Prior malignancy (except nonmelanomatous skin cancer) unless disease free for a minimum of 2 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.

3. Known CNS lymphoma.

4. Prior or current treatment with certain medications. Talk to Study Contact for specifics.

5. Subject is at high risk for TLS.

6. Subject has malabsorption syndrome or other condition which may affect an enteral route of administration.

7. Subject has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase.

8. Significant history of heart disease.

9. Subject has an active infection.

10. Known active Hepatitis B or Hepatitis C.

11. A serious uncontrolled medical disorder that in the opinion of the investigator would impair the ability of the subject to receive protocol therapy.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Recurrent Lymphoma, Mantle-Cell

Intervention

Drug:
• ABT-199 and Ibrutinib Combination
Both are administered orally once daily.

Locations

Country	Name	City	State
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	University of Virginia	Charlottesville	Virginia
United States	City of Hope	Duarte	California
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Craig Portell, MD	AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities		30 Days Following Start of Treatment
Secondary	Incidence and Severity of Adverse Events		Through 30 Days Following the Last Treatment
Secondary	Overall Response Rate		Every Year Until Death; an Average of 2 Years
Secondary	Complete Response Rate		Every Year Until Death; an Average of 2 Years
Secondary	Progression-Free Survival		Every Year Until Death; an Average of 2 Years
Secondary	Overall Survival		Every Year Until Death; an Average of 2 Years