Clinical Trials /

Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

NCT03518112

Description:

The goal of this clinical research study is to learn if blinatumomab given in combination with low-intensity chemotherapy can help to control Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL). The safety and effectiveness of this combination will also be studied. This is an investigational study. Blinatumomab is FDA approved and commercially available for the treatment of other types of ALL. The chemotherapy used in this study is FDA approved and commercially available for the treatment of ALL. It is considered investigational to use blinatumomab in combination with chemotherapy to treat Ph- ALL. The study doctor can explain how the study drugs are designed to work. Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)
  • Official Title: Phase II Study of the Combination of Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Clinical Trial IDs

  • ORG STUDY ID: 2017-0127
  • SECONDARY ID: NCI-2018-00737
  • NCT ID: NCT03518112

Conditions

  • Leukemia
  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
CyclophosphamideCytoxan, NeosarBlinatumomab + Mini-Hyper-CVD
MesnaMesnexBlinatumomab + Mini-Hyper-CVD
VincristineBlinatumomab + Mini-Hyper-CVD
DexamethasoneDecadronBlinatumomab + Mini-Hyper-CVD
G-CSFFilgrastim, NeupogenBlinatumomab + Mini-Hyper-CVD
MethotrexateBlinatumomab + Mini-Hyper-CVD
CytarabineAra-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochlorideBlinatumomab + Mini-Hyper-CVD
RituximabRituxanBlinatumomab + Mini-Hyper-CVD
BlinatumomabBlinatumomab + Mini-Hyper-CVD

Purpose

The goal of this clinical research study is to learn if blinatumomab given in combination with low-intensity chemotherapy can help to control Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL). The safety and effectiveness of this combination will also be studied. This is an investigational study. Blinatumomab is FDA approved and commercially available for the treatment of other types of ALL. The chemotherapy used in this study is FDA approved and commercially available for the treatment of ALL. It is considered investigational to use blinatumomab in combination with chemotherapy to treat Ph- ALL. The study doctor can explain how the study drugs are designed to work. Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Drug Administration:

      This study has 3 parts:

        -  Induction--the part of the study in which the study drugs are designed to create a
           response from the disease. Induction will take place during Cycle 1 of the study. An
           Induction cycle is about 42 days (6 weeks).

        -  Consolidation--the part of the study in which the drugs are designed to continue to
           cause the disease to respond. Consolidation will take place during Cycles 2-4. Each
           consolidation cycle is about 42 days (6 weeks).

        -  Maintenance--the part of the study in which chemotherapy is given to help keep the
           disease under control. Maintenance will take place after Consolidation and will last for
           up to 2 years. Each maintenance cycle is 4 weeks.

      If you are found to be eligible to take part in this study, you will receive a central venous
      catheter (CVC) if you do not already have one. A CVC is a sterile flexible tube that will be
      placed into a large vein while you are under local anesthesia. Your doctor will explain this
      procedure to you in more detail, and you will be required to sign a separate consent form for
      this procedure.

      Negative days are the days before the start of a cycle. While on this study, you will need to
      be hospitalized on Days -3 to 6 of each cycle. In addition, you will need to stay in the
      hospital on Day 21 of Cycle 1 and Days 1 and 2 of Cycle 2.

      You will receive blinatumomab by vein continuously (nonstop) on Days 1-28 of Cycles 1-4. You
      will not take blinatumomab on Days 29-42. Blinatumomab will be delivered by a small pump,
      which you will carry with you for the whole time you receive the drug. This allows you to
      receive the drug constantly over a long period of time. You will be given a shoulder or belt
      bag to hold the pump and infusion bag. You will be able to wear regular clothes, walk around,
      and perform daily living activities. You will be given instructions for taking a shower and
      other activities. However, because the line must be kept free of infection and connected to
      the pump at all times, some activities (like swimming) are not allowed during the study. The
      study staff will give you more information on activities you should not do while receiving
      the drug.

      For blinatumomab doses where you are not hospitalized, you will need to return to the clinic
      at certain times (about every 48 hours) to have the infusion bag changed. The study staff
      will tell you how often the infusion bag must be changed. If the infusion is stopped for more
      than 4 hours, you may need to return to the clinic to have the infusion started again.

      You will receive dexamethasone by mouth or by vein about 1 hour before the start of the
      blinatumomab dose on Day 1 of Cycles 1-4, within 1 hour after any time your dose is raised
      (such as Day 5 of Cycle 1), Maintenance Therapy Cycles 6 and 12, and if your infusion has to
      be stopped for more than 4 hours. You will also take dexamethasone on the schedule listed
      below. Dexamethasone is given to prevent side effects associated with blinatumomab treatment.
      If side effects do occur, you will receive additional dexamethasone by mouth or by vein. When
      you are hospitalized, you will receive dexamethasone by vein over about 30 minutes. When you
      are at home, you will take it by mouth.

      You may be given other drugs to help prevent side effects. The study staff will tell you
      about these drugs, how they will be given, and the possible risks.

      Cycles 1-4 will take place in 2 parts: Part A and Part B. Part A will take place from Days 1-
      21 of each cycle. Part B will take place from Days 22-42 of each cycle. All participants will
      receive this treatment.

        -  During Part A, you will receive mini-hyper-CVD chemotherapy. This is a combination of
           the drugs G-CSF or pegfilgrastim, cyclophosphamide, mesna, dexamethasone, methotrexate,
           cytarabine, and vincristine.

        -  During Part B, you will receive MTX-ARA-C chemotherapy. This is a combination of the
           drugs methotrexate and cytarabine. If needed, you will also receive leucovorin and
           rituximab.

      Part A Dose Administration:

      During Cycle 1:

        -  Depending on what your insurance allows, you will either receive G-CSF each day as an
           injection under the skin until your blood counts recover or on Day 1 you will receive
           pegfilgrastim as an injection under the skin 1 time each cycle.

        -  On Days -3 to -1, you will receive cyclophosphamide 2 times each day (about 12 hours
           apart) by vein over about 3 hours.

        -  On Days -3 to -1, you will receive mesna by vein continuously (nonstop) for about 36
           hours to help prevent side effects related to cyclophosphamide.

        -  On Day 2, you will receive methotrexate intrathecally (by spinal tap).

        -  On Day 7, you will receive cytarabine intrathecally.

        -  On Days 0 and Day 7, you will receive vincristine by vein over 15 minutes.

        -  On Days -3 to 0 and Days 7-10, you will receive dexamethasone by mouth or by vein.

        -  If the doctor thinks it is needed, on Days -3 and 0, you will receive rituximab by vein
           over 4-6 hours.

      During Cycles 2-4:

        -  On Days 1-3, you will receive cyclophosphamide 2 times each day (about 12 hours apart)
           by vein over about 3 hours.

        -  On Days 1-3, you will receive mesna by vein continuously (nonstop) for about 72 hours to
           help prevent side effects related to cyclophosphamide.

        -  On Day 4 and Day 11, you will receive vincristine by vein over 15 minutes.

        -  On Day 5, you will receive G-CSF as an injection under the skin or, you will receive
           pegfilgrastim as an injection under the skin until your blood counts recover.

        -  On Days 2, you will receive methotrexate intrathecally.

        -  On Days 7, you will receive cytarabine intrathecally.

        -  On Days 1-4 and Days 11-14, you will receive dexamethasone by mouth or by vein.

        -  If the study doctor thinks it is needed, on Day 1 and Day 8 of Cycle 2, you may receive
           rituximab by vein over 4-6 hours.

      Part B Dose Administration:

      During Cycles 1-4:

        -  Depending on what your insurance allows, you will either receive G-CSF each day as an
           injection under the skin until your blood counts recover or you will receive
           pegfilgrastim as an injection under the skin on Day 25.

        -  On Day 22, you will receive methotrexate by vein over about 24 hours.

        -  On Days 23 and 24, you will receive cytarabine by vein 2 times each day (about 12 hours
           apart) over about 3 hours for a total of 4 doses.

        -  If the doctor thinks it is needed, you may receive leucovorin by vein over about 15
           minutes or by mouth 4 times a day for up to 8 doses, beginning 12 hours after the
           methotrexate dose ends to help reduce the risk of side effects. The study staff will
           tell you which way you will receive leucovorin.

        -  If the study doctor thinks it is needed, On Days 22 and 29 of Cycles 1 and 2, you may
           receive rituximab by vein over about 4 to 6 hours.

      Maintenance Therapy (Cycles 1-24):

      Each maintenance cycle will last about 28 days, except Cycles 6 and 12. Cycles 6 and 12 will
      be about 42 days. The exact length will depend on how your body responds to the chemotherapy.

      After your last consolidation cycle (Cycle 4), if the disease has not gotten worse, you will
      start Maintenance Therapy. During Maintenance Therapy, you will receive the following drugs
      for about 2 years:

        -  On Days 1-5 of Cycles 1-5, 7-11, and 13-24 you will take prednisone by mouth.

        -  On Day 1 of Cycles 1-5, 7-11, and 13-24 you will receive vincristine by vein 1 time over
           about 15 minutes.

        -  On Days 1-28 of Cycles 1-5 and 7-11, you will receive 6-MP twice a day

        -  You will receive methotrexate by mouth 1 time each week of Cycles 1-5 and 7-11.

        -  On Days 1-28 of Cycles 6 and 12, you will receive blinatumomab by vein continuously.
           °You will need to return to the hospital for days 1-6 of Cycle 6.

        -  For blinatumomab doses where you are not hospitalized, you will need to return to the
           clinic at certain times (about every 48 hours) to have the infusion bag changed.

      Length of Treatment:

      You may receive up to 4 cycles of mini-hyper-CVD, MTX-ARA-C, and blinatumomab followed by 24
      cycles of chemotherapy-based maintenance treatment. You will no longer be able to take the
      study drugs if the disease gets worse, if intolerable side effects occur, or if you are
      unable to follow study directions.

      Your participation in this study will be over after follow-up (described below).

      Study Visits:

      If it is more convenient for you, you may have some of the following tests/procedures
      performed at your local doctor's office or clinic. Your local doctor will tell the study
      doctor at MD Anderson the results of the testing. The study doctor and/or study staff will
      discuss this option with you.

      At least 1 time each week during Cycles 1-4, then every 4-6 weeks during Maintenance, blood
      (about 2-3 tablespoons) will be drawn for routine tests.

      On Days 1 and 14 of Cycles 1-4, Day 28 of Cycle 4, and Days 1 and 14 of Cycles 6 and 12 of
      Maintenance therapy, blood (about 1-2 teaspoons) will be drawn to check the status of the
      disease and for immune system testing.

      On Day 21 of Cycles 1-4, you will have a chest x-ray.

      On Days 21 and 42 of Cycle 1, Day 42 of Cycle 2 depending on the status of the disease, and
      Day 42 of Cycle 4, and at any point during Maintenance that your doctor thinks it is needed,
      you will have a bone marrow biopsy and/or aspiration to check the status of the disease, for
      cytogenetic and immune system testing.

      On Day 42 of Cycle 2, you will have an ECHO or a MUGA scan to check your heart function.

      Every 3-6 months during Maintenance Cycles, blood (about 1-2 teaspoons) will be drawn to
      check the status of the disease and for immune system testing.

      Long-Term Follow-Up:

      About 30 days after your last dose of study drugs and then about every 3 months for 1 year
      and then about every 6 months after that from then on, you will be called by a member of the
      study staff and asked how you are doing and if you have started any new medications. Each
      call should last about 10 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
Blinatumomab + Mini-Hyper-CVDExperimentalBlinatumomab given in combination with mini-hyper-CVD. Each cycle of induction and consolidation is 42 days. Mini-hyper-CVD chemotherapy regimen consists of a total of 8 cycles with mini-hyper-CVD alternating with high-dose methotrexate and cytarabine administered approximately every 21 days. A total of 4 cycles of blinatumomab are planned in induction/consolidation and 2 additional cycles during maintenance. Blinatumomab given by continuous infusion for 4 weeks, followed by a 2 week treatment-free period. Patients then receive 2 years of maintenance therapy with POMP (6-mercaptopurine [6-MP], vincristine, methotrexate and prednisone) and blinatumomab single agent given in cycles 6 and 12 of the first year and vincristine and prednisone alone for an additional year.
  • Cyclophosphamide
  • Mesna
  • Vincristine
  • Dexamethasone
  • G-CSF
  • Methotrexate
  • Cytarabine
  • Rituximab
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients >/= 18 years of age with first or second relapsed/refractory B-cell ALL.

          2. Performance status </=3 (ECOG Scale)

          3. Adequate liver function as defined by the following criteria: Total serum bilirubin
             </= 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or
             the underlying leukemia approved by the PI; Alanine aminotransferase (ALT) </= 3 x
             ULN, unless due to the underlying leukemia approved by the PI; Aspartate
             aminotransferase (AST) </= 3 x ULN unless due to the underlying leukemia approved by
             the PI or Aspartate aminotransferase (AST) </= 3 x ULN unless due to the underlying
             leukemia approved by the PI

          4. Signed informed consent

          5. Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP
             must agree to use contraception during the study, if sexually active.

        Exclusion Criteria:

          1. Patients with Ph-positive ALL or Burkitt leukemia

          2. Active, uncontrolled central nervous system (CNS) leukemia involvement

          3. Active serious infection not controlled by oral or intravenous antibiotics.

          4. Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or
             squamous cell carcinoma) that in the investigator's opinion will shorten survival to
             less than 1 year.

          5. Known hepatitis B or C infection, or known seropositivity for HIV

          6. Active Grade III-V cardiac failure as defined by the New York Heart Association
             Criteria.

          7. Patients with a cardiac ejection fraction (as measured by either MUGA or
             echocardiogram) <40%

          8. Prior history of treatment with blinatumomab

          9. Treatment with any investigational antileukemic agents or chemotherapy agents in the
             last two weeks, unless full recovery from side effects has occurred or patient has
             rapidly progressive disease judged to be life-threatening by the investigator.

         10. Pregnant and lactating women will not be eligible; women of childbearing potential
             should have a negative pregnancy test prior to entering on the study and be willing to
             practice methods of contraception. Women do not have childbearing potential if they
             have had a hysterectomy or are postmenopausal without menses for 12 months. In
             addition, men enrolled on this study should understand the risks to any sexual partner
             of childbearing potential and should practice an effective method of birth control.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event Free Survival (EFS)
Time Frame:2 years
Safety Issue:
Description:Event free survival (EFS) defined as no response, loss of response, or death.

Secondary Outcome Measures

Measure:Relapse-Free Survival
Time Frame:2 years
Safety Issue:
Description:Relapse-free survival is the time from documented complete response until relapse or death.
Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:Overall response rate defined as the percentage of patients achieving CR or CRi
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall survival defined as the time from the first day of treatment to time of death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Leukemia
  • Acute Lymphoblastic Leukemia
  • ALL
  • Relapsed/Refractory
  • Philadelphia Chromosome Negative
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Mesna
  • Mesnex
  • Vincristine
  • Dexamethasone
  • Decadron
  • G-CSF
  • Filgrastim
  • Neupogen
  • Methotrexate
  • Cytarabine
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Rituximab
  • Rituxan
  • Blinatumomab

Last Updated