Standard Maintenance POMP/D Plus Ixazomib Maintenance Therapy in Adult Patients With Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma or Mixed Phenotype Acute Leukemia in Complete Remission (CR)

NCT02578511 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: PRO25835
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase I study, escalating doses of IXAZOMIB will be combined with the POMP/D regimen.

Conditions

Acute Lymphoblastic Leukemia in Complete Remission; Lymphoblastic Lymphoma in Complete Remission; Mixed Phenotype Acute Leukemia in Complete Remission

Keywords

Acute Lymphoblastic Leukemia in Complete Remission; Lymphoblastic Lymphoma in Complete Remission; Mixed Phenotype Acute Leukemia in Complete Remission; IXAZOMIB; POMP/D; Phase I; Early Phase; Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Mixed Phenotype Acute Leukemia; ALL

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of ixazomib with POMP/D maintenance

  The patient cohort enrolled at each dose level will be monitored for dose-limiting toxicity for eight weeks prior to enrolling the next cohort of patients at a new dose level. Subsequent patient cohorts will be enrolled at doses according to the CRM design. A maximum sample size of 12 patients will be enrolled over four potential doses to determine the maximum tolerated dose of ixazomib with POMP/D maintenance. Adverse events will be summarized with descriptive statistics at each dose level of ixazomib.

  Eight (8) weeks

Secondary Outcomes (1)

• Progression-free survival of patients treated with oral Ixazomib and standard maintenance regimen.

  Three (3) years

Study Arms (1)

Ixazomib (MLN9708) in combination with standard POMP/D

EXPERIMENTAL

Patients who are receiving maintenance therapy with the POMP/D (Methotrexate, 6-Mercaptopurine, Vincristine, Prednisone/Dexamethasone) will be enrolled. Each cycle will be 28 days. The patients will receive IV vincristine, dexamethasone or prednisone, methotrexate and 6 - Mercaptopurine. Ixazomib will be administered on days 1, 8 and 15. Both prednisone and dexamethasone are acceptable drugs in maintenance therapy. For example, in the HyperCVAD regimen or the CALGB 8811 prednisone is used. Patients will continue the same maintenance regimen they are receiving and ixazomib will be added to that.

Drug: Ixazomib

Interventions

Ixazomib DRUG

Patients who have been on stable doses of 6 - MP, vincristine, and methotrexate for a minimum of eight weeks and have at least six months remaining of maintenance are eligible to receive Ixazomib, which will be administered on days 1, 8 and 15.

Ixazomib (MLN9708) in combination with standard POMP/D

Eligibility Criteria

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

You may qualify if:

• Male or female patients 18 years or older.
• Have B-precursor, T cell ALL, MPAL or LBL in CR following therapy and receiving maintenance therapy. Patients with persistent minimal residual disease and/or in complete remission with incomplete platelet recovery are not eligible.
• Prior therapy: Should have achieved CR following the induction and intensification phases of treatment, with no limit on the number of prior treatment regimens, and started treatment with POMP/D maintenance. Patients who achieved CRp or CR with persistence of minimal residual disease are not eligible.
• Patients are eligible after allogeneic stem cell transplantation.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must meet the following clinical laboratory criteria:
• Total bilirubin \< 1.5 X the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase. (AST) \< 3 X ULN.
• Calculated creatinine clearance \> 30 mL/min.
• Absolute neutrophil count (ANC) \> 1,000/cmm and platelets \> 75,000/cmm.
• Patient has a life expectancy of at least six months.
• Patients must be at least two weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments.
• Patients should be on stable doses of 6-mercaptopurine, methotrexate, vincristine and prednisone/dexamethasone as part of the POMP/D regimen, for a minimum of eight weeks PRIOR to starting ixazomib treatment.
• Patients should have at least six months of therapy with the POMP/D regimen remaining prior to starting IXAZOMIB (MLN9708).
• Female patients who:

You may not qualify if:

• Systemic treatment, within 14 days before study enrollment, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of ginkgo biloba or St. John's wort.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements. Patients should not have evidence of active infection.
• Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or GI procedure that could interfere with the oral absorption or tolerance of treatment.
• Active chronic graft vs. host disease requiring therapy.
• Patient has ≥ grade 2 peripheral neuropathy.
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the trial start and throughout the duration of this trial.
• Failure to have fully recovered (i.e., \< grade 1 toxicity) from the reversible effects of prior chemotherapy.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past six months.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with treatment completion according to this protocol.
• Known allergy to any of the study medications, their analogues or excipients in the various formulations of any agent.
• Diagnosed or treated for another malignancy within two years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Female patients who are breastfeeding or have a positive serum pregnancy test during the screening.

Sponsors & Collaborators

• Ehab L Atallah: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ehab Atallah, MD

  Medical College of Wisconsin

  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: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Department of Medicine

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 19, 2015
• Study Start: June 29, 2017
• Primary Completion: February 13, 2018
• Study Completion: February 13, 2018
• Last Updated: February 15, 2018

Record last verified: 2018-02

Locations

US (1)