Phase 2
N=43
A Study of Ixazomib and Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma
Mantle-Cell Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT03323151 ↗Enrolled (actual)
43
Serious AEs
46.5%
Results posted
Jan 2024
Primary outcome: Primary: Phase I: Dose Limiting Toxicities (DLT) Rate — 3; 5; 0; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Ixazomib (Drug); Ibrutinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- PrECOG, LLC.
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I: Dose Limiting Toxicities (DLT) Rate |
3; 5; 0; 1; 0; 3 | — |
| PRIMARY Phase II: Complete Response Rate |
0; 11; 2; 10; 1; 0 | — |
| SECONDARY Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 |
0; 0; 0; 1; 0; 1 | — |
| SECONDARY Overall Response Rate (ORR) |
2; 6; 2; 21; 1; 3 | — |
| SECONDARY Progression-Free Survival (PFS) |
17.12; 27.43; 14.16; 29.83 | — |
| SECONDARY Overall Survival (OS) |
27.01; 47.74; 29.17; 35.68 | — |
Summary
Patients with mantle cell lymphoma (MCL) that has relapsed (come back) or refractory (progressed on treatment) will receive ixazomib and ibrutinib.
Ibrutinib has been approved by the Food and Drug Administration (FDA) as treatment for patients with mantle cell lymphoma who have received at least one prior therapy.
Ixazomib is in a class of medications called proteasome inhibitors. Cancer cells depend on proteasome to provide this protein metabolism (turnover) function to regulate their growth and survival. Ixazomib disrupts a cancer cells' ability to survive by blocking the proteasome and disrupting protein metabolism. This may help to slow down the growth of cancer or may cause cancer cells to die.
The purpose of this study is to see whether the addition of ixazomib to ibrutinib chemotherapy is effective in treating people who have relapsed or refractory MCL and to examine the side effects associated with ixazomib in combination with ibrutinib.
Eligibility Criteria
- Relapsed or refractory, pathologically proven mantle cell lymphoma. Must have a current or prior tissue sample that is IHC positive for cyclin D 1 or that is positive by FISH or cytogenetics for t(11;14).
- Must have been refractory to and/or relapsed/progressed after at least 1 prior therapy.
- Prior autologous or allogeneic transplant are allowed. Patients may not have active grade II-IV acute graft-versus-host disease (GVHD) or moderate/severe chronic GVHD by NIH criteria and may not require immunosuppressive medications and/or corticosteroids for the management of acute or chronic GVHD.
- Phase I: Prior proteasome inhibitor and/or Bruton's tyrosine kinase (BTK) inhibitors are allowed but patients may not have been exposed to the combination of proteasome inhibitor and BTK inhibitor. Patients who have progressed on ibrutinib that are felt to be at high risk for rapid progression on this study shall not be eligible for the phase I portion of the study. NOTE: Ibrutinib pre-treated patients must meet all eligibility criteria AND must have discontinued prior ibrutinib at least 3 months prior to starting study therapy. PHASE I COMPLETED NOVEMBER 25, 2019.
- Phase II: Prior proteasome inhibitors allowed. (Please note prior to Version 3.0 of the protocol prior proteasome inhibitor and/or Bruton's tyrosine kinase inhibitors were allowed but patients could not have been exposed to the combination of proteasome inhibitor and BTK inhibitor).
- Age ≥ 18 years.
- Eastern Oncology Oncology Group (ECOG) performance status of 0-2.
- Ability to understand and willingness to sign Institutional Review Board (IRB)-approved informed consent.
- Willing to provide archived tumor tissue, bone marrow (if sufficient bone marrow and tumor tissue are available) and blood samples for research.
- Adequate organ function as measured by the following criteria
- Absolute Neutrophil Count (ANC) ≥ 750/mm³
- Platelets ˃50,000/mm³
- Serum Creatinine ≤ 2x Upper Limit Normal (ULN)
- ALT and AST ≤ 3x ULN
- Total Bilirubin ≤ 1.5x ULN
- Patients must not have received systemic treatment for MCL for at least 14 days prior to enrollment, except for steroids which may be used to manage acute symptoms related to disease up to 48 hours prior to starting study therapy. Radiation therapy must be concluded at least 14 days prior to enrollment.
- Women must not be pregnant or breastfeeding since we do not know the effects of ixazomib and ibrutinib on the fetus or breastfeeding child. All sexually active females of childbearing potential must have a blood test to rule out pregnancy within 2 weeks prior to registration.
- Sexually active women of child-bearing potential with a non-sterilized male partner and sexually active men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation, and for 3 months following last dose of study drugs.
- Patients must have resolved all prior non-hematologic toxicities assessed as related to prior therapy to ≤ grade 1.
- Patients must have measurable disease (i.e., ≥ 1.5 cm in largest diameter) by conventional imaging modalities. Patients with extranodal involvement as the only measurable site of disease must have a largest diameter ≥ 1.0 cm and must be attributable to active lymphoma in the opinion of the investigator.
- Patients may not have current/active Central Nervous System (CNS) involvement with mantle cell lymphoma (patients with prior CNS involvement are eligible as long as they have had no evidence of active CNS disease for at least 6 months).
- Patients may not have another malignancy that could interfere with the evaluation of safety or efficacy of this combination. Patients with a prior malignancy will be allowed without study chair approval in the following circumstances:
- Not currently active and diagnosed at least 3 years prior to the date of enrollment.
- Non-invasive diseases such as low risk cervical can
Data sourced from ClinicalTrials.gov (NCT03323151). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.