Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults

NCT02228772 | Completed Phase 1 DMC

• 1 other identifier: 14-200
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is evaluating a combination of drugs considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new drug called MLN 9708. Additionally, the study is also evaluating if bone marrow or stem cell transplantation, which will be given to some participants, helps to prevent ALL from returning.

Conditions

Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic Leukemia; Lymphoblastic lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum Dose Tolerated of MLN 9708

  2 Years

Secondary Outcomes (5)

• Percentage of Patient with Complete Remission (CR) rate at the end of induction therapy

  30 Days

• Percentage of Participants with Disease Free Survival

  2 Years

• Rate of Overall survival (OS)

  1 Year, 2 Year, 3 Year

• Complete Remission Rate

  2 Years

• Rate of Toxicity

  2 Years

Study Arms (1)

MLN 9708

EXPERIMENTAL

* Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * MLN 9708 will be given with standard multi-drug regimen for ALL . MLN 9708 will be administered on determined days during Induction therapy cycle and Consolidation cycle. If remission occurs and if eligible, the next stage with be either Stem Cell or Bone Marrow Transplant. * If not eligible to receive a transplant, the participant will continue on this study for the next 3 stages. * CNS Therapy * Consolidation 2 * Continuation Therapy No further MLN9708, the investigational drug, will be given after Consolidation 1 Standard chemotherapy -Vincristine, Cytarabine, Doxorubicin, Mercaptopurine, Cyclophosphamide, Methotrexate

Drug: MLN 9708; Drug: Vincristine; Drug: Cytarabine; Drug: Doxorubicin; Drug: Mercaptopurine; Drug: Cyclophosphamide; Drug: Methotrexate

Interventions

MLN 9708 DRUG

Patients will received standard chemotherapy as well as MLN 9708 in escalating doses.

Also known as: Ixazomib

MLN 9708

Vincristine DRUG

Standard chemotherapy dosage and duration

Also known as: Oncovin, Vincasar PFS, Vincrex, Vincristine sulfate, VCR

MLN 9708

Cytarabine DRUG

Standard chemotherapy dosage and duration

Also known as: Ara-C, Cytosar-U, Cytosine arabinoside

MLN 9708

Doxorubicin DRUG

Standard chemotherapy dosage and duration

Also known as: Adriamycin, Rubex

MLN 9708

Mercaptopurine DRUG

Standard chemotherapy dosage and duration

Also known as: 6-MP, Purinethol, Purixan

MLN 9708

Cyclophosphamide DRUG

Standard chemotherapy dosage and duration

Also known as: Cytoxan, Neosar, CTX

MLN 9708

Methotrexate DRUG

Standard chemotherapy dosage and duration

Also known as: Folex, Mexate, MTX, Methotrex (formerly Amethopterin)

MLN 9708

Eligibility Criteria

• Age: 51 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8).
• Patients with mature B-cell ALL will be removed from the protocol as soon as that diagnosis is made and should be treated on a B-cell leukemia (Burkitt's) protocol. NOTE: Patients with T-cell surface markers and a t(8;14)(q24;q11) remain eligible.
• Patients with lymphoblastic lymphoma are also eligible
• No prior anti-leukemic therapy except the following are allowed: \<1 week of corticosteroids, or hydroxyurea or emergent leukopheresis. Longer steroid use for diseases other than leukemia is permitted.
• Age 51- 75 years
• Voluntary written consent must be given before performance of any study-related procedures 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.
• If patient is known to be HIV positive, they will not be eligible for the protocol. HIV testing is not mandatory prior to protocol enrollment.
• Patients whose comorbid medical condition, in the investigator's opinion, would make participation in this trial and adherence to the protocol guidelines difficult should be excluded.
• Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely are excluded.
• Ejection fraction ≥ 45%
• Creatinine\<2.0 times upper limit of normal
• ECOG performance status of 0, 1, 2
• Non pregnant and non lactating Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Radiotherapy within 14 days before enrollment. Radiotherapy is excluded during induction and consolidation 1 while receiving MLN 9708.
• 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.
• Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. Hepatitis and HIV testing are not required prior to the start of treatment.
• 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.
• Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
• 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 nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21days of the start of this trial and throughout induction and consolidation 1 portions of this trial (while on MLN 9708). Patients may enroll in transplant and post transplant studies after consolidation 1 treatment (See Section 6.5).
• Systemic treatment, within 14 days before the first dose of MLN9708, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort. Ciprofloxocin should not be administered for at least 2 days before MLN 9708 administration. Extended release ciprofloxocin should not be administered for at least 3 days prior to MLN 9708 administration.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ixazomib; Vincristine; Cytarabine; Doxorubicin; Mercaptopurine; Cyclophosphamide; Methotrexate; merphos

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

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Sulfhydryl Compounds; Sulfur Compounds; Purines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines

Study Officials

• Philip Amrein, MD

  Massachusetts General Hospital

  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: August 23, 2014
• First Posted: August 29, 2014
• Study Start: December 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: November 1, 2019
• Last Updated: November 26, 2019

Record last verified: 2019-11

Locations

US (3)