Ixazomib & Rituximab After Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma in Remission

NCT02632396 | Unknown Phase 1 DMC

• 5 other identifiers: IRB00076016NCI-2015-01943X16058Winship2839-15P30CA138292
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the side effects and best dose of ixazomib citrate (ixazomib) when given together with rituximab and to see how well they work after stem cell transplant in treating patients with mantle cell lymphoma that are no longer showing signs or symptoms of cancer. Ixazomib may stop the growth of cancer cell by blocking enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving ixazomib together with rituximab after transplant may help prevent the cancer from coming back.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose of ixazomib, defined as the dose where 1 or fewer of 6 treated patients experience a dose limiting toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Phase I)

  28 days

• Progression-free survival (PFS), defined as the percentage of patients who have received at least one dose of study therapy who are alive and free of disease progression or relapse at 1-year post autologous stem cell transplant (Phase II)

  Determined using the Kaplan-Meier method.

  1 year

Secondary Outcomes (9)

• Conversion rate from MRD positive to MRD negative during therapy (Phase I & II)

  Up to 10 months (10 courses of treatment)

• Incidence of adverse events graded according to CTCAE version 4.03 (Phase I & II)

  Up to 30 days after administration of the last dose of study treatment

• Median OS (Phase II)

  Up to 2 years

• Median PFS (Phase II)

  Up to 2 years

• Overall survival (OS) (Phase II)

  1 year

Other Outcomes (4)

• Median OS for patients who have a pre-transplant PET/CT (Phase II)

  Up to 2 years

• Median PFS for patients who have a pre-transplant PET/CT (Phase II)

  Up to 2 years

• PFS for patients who have a pre-transplant PET/CT (Phase II)

  1 year

Study Arms (1)

Treatment (ixazomib, rituximab)

EXPERIMENTAL

Beginning between 70-180 days after stem cell transplant, patients receive ixazomib PO on days 1, 8, and 15, and rituximab IV (or SC after first dose if deemed appropriate) on day 1 of courses 1, 3, 5, 7, and 9. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Drug: Ixazomib; Biological: Rituximab

Interventions

Ixazomib DRUG

Given PO

Also known as: Ninlaro, MLN9708, Ixazomib Citrate

Treatment (ixazomib, rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: Rituxan, MabThera, Chimeric Anti-CD20 Antibody

Treatment (ixazomib, rituximab)

Eligibility Criteria

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

You may qualify if:

• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• Patients must have a diagnosis of mantle cell lymphoma confirmed at diagnosis by one of the following:
• t(11;14) detected by fluorescence in situ hybridization (FISH), conventional cytogenetics, or other molecular evaluation
• Expression of cyclin D1 confirmed by immunohistochemistry.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Patients must have completed an autologous stem cell transplant after their first course of treatment; patients who have relapsed or progressed at any time prior to transplant are not eligible.
• Patients must not have experienced confirmed progressive disease since the time of their transplant.

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Failure to have fully recovered (ie, ≤ grade 1 toxicity) from the reversible effects of prior chemotherapy, except for laboratory abnormalities which are addressed above.
• Major surgery within 14 days before enrollment.
• Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.
• Central nervous system involvement with lymphoma at any time in the patient's history; intrathecal prophylaxis during induction is allowed as long as active disease has not been identified.
• Infection requiring intravenous antibiotic therapy or other serious infection within 14 days before study enrollment.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; patients experiencing an isolated cardiac complication at the time of transplant who have been evaluated by cardiology and remained stable for at least 60 days are eligible.
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong cytochrome P450, family 3, subfamily A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. Patients who have previously tested positive for hepatitis B core antibody may be eligible if they are confirmed to NOT have active disease and are on appropriate anti-viral therapy. No additional hepatitis or HIV testing is required for patients who have been evaluated during their induction and/or pre-transplant work-up and have had no clinical evidence of HIV, hepatitis B or hepatitis C since their last evaluation.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. Patients with a prior reaction to rituximab are permitted if the investigator feels that this reaction is manageable with standard supportive care measures and would otherwise be comfortable administering rituximab outside of the clinical trial setting.
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing; patients with known GI involvement with mantle cell lymphoma who have no clinical evidence of active disease at the time of enrollment are eligible.
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with non-melanoma skin cancer, carcinoma in situ of any type, or low risk cervical cancer are not excluded if they have undergone complete resection and are deemed free of disease by their treating physician; patients with low risk prostate cancer who are under observation are eligible if their urologist or oncologist does not expect them to require therapy within 1 year.
• Patient has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period.
• Receipt of therapy on a clinical trial, including investigational and non-investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial; participation on non-therapeutic clinical studies is allowed, and patients who participated on a clinical trial for induction and/or transplant but who have completed the prescribed therapy course for that study and have been off therapy for at least 30 days are eligible.

Sponsors & Collaborators

• Emory University: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Related Publications (1)

• Romancik JT, Chen Z, Allen PB, Waller EK, Valla K, Colbert A, Rosand C, Palmer AF, Flowers CR, Cohen JB. Ixazomib With or Without Rituximab Following Maintenance Autologous Stem Cell Transplant in Mantle Cell Lymphoma: A Single-Center Phase I Trial. Clin Lymphoma Myeloma Leuk. 2022 Dec;22(12):e1084-e1091. doi: 10.1016/j.clml.2022.08.013. Epub 2022 Aug 24.

  PMID: 36180329 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ixazomib; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; 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

Study Officials

• Jonathon Cohen, MD, MS

  Emory University/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 14, 2015
• First Posted: December 16, 2015
• Study Start: March 1, 2016
• Primary Completion: August 15, 2023
• Study Completion: August 1, 2024
• Last Updated: May 9, 2023

Record last verified: 2023-05

Locations

US (2)