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Trial record 1 of 1 for:    NCT03518112
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Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

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ClinicalTrials.gov Identifier: NCT03518112
Recruitment Status : Recruiting
First Posted : May 8, 2018
Last Update Posted : August 16, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Leukemia Acute Lymphoblastic Leukemia Drug: Cyclophosphamide Drug: Mesna Drug: Vincristine Drug: Dexamethasone Drug: G-CSF Drug: Methotrexate Drug: Cytarabine Drug: Rituximab Drug: Blinatumomab Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 18, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Blinatumomab + Mini-Hyper-CVD

Blinatumomab 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.

Drug: Cyclophosphamide

Phase 1A: Cyclophosphamide 150 mg/m2 by vein every 12 hours for 6 doses Days -3, -2, -1.

Phase 2A to 4A: Cyclophosphamide 150 mg/m2 by vein every 12 hours for 6 doses Days 1, 2, 3.

Other Names:
  • Cytoxan
  • Neosar

Drug: Mesna

Phase 1A: Mesna 300 mg/m2/d by vein continuous infusion daily for 24 hours, starting approximately 1 hour prior to Cyclophosphamide and completing by approximately 12 hours after the last dose of Cyclophosphamide.

Phase 2A to 4A: Mesna 300 mg/m2/d by vein continuous infusion daily for 24 hours, starting approximately 1 hour prior to Cyclophosphamide and completing by approximately 12 hours after the last dose of Cyclophosphamide.

Other Name: Mesnex

Drug: Vincristine

Phase 1A: Vincristine 2 mg by vein on Day 0 and Day 7.

Phase 2A to 4A: Vincristine 2 mg by vein on Day 1 and Day 11.


Drug: Dexamethasone

Phase 1A: Dexamethasone 20 mg by vein or by mouth daily on Days -3 to 0 and Days 7-10.

Phase 2A to 4A: Dexamethasone 20 mg by vein or by mouth daily on Days 1-4 and Days 11-14.

Other Name: Decadron

Drug: G-CSF

Phase 1A: G-CSF 10 mcg/kg (rounded) subcutaneously Daily (or 5 mcg/kg twice daily) until post-nadir granulocytes > 1.0 x 109/L.

Phase 2A to 4A: G-CSF 10 mcg/kg (rounded) subcutaneously Daily (or 5 mcg/kg twice daily) until post-nadir granulocytes > 1.0 x 109/L.

Phase 1B to 4B: G-CSF 10 mcg/kg (rounded) subcutaneously Daily (or 5 mcg /kg twice daily) until post-nadir granulocytes ≥ 1.0 x 109/L.

Other Names:
  • Filgrastim
  • Neupogen

Drug: Methotrexate

Phase 1A: Methotrexate 12 mg intrathecally (6 mg via Ommaya reservoir) on Day -2.

Phase 2A to 4A: Methotrexate 12 mg intrathecally (6 mg via Ommaya reservoir) on Day 2.

Phase 1B to 4B: Methotrexate 50 mg/m2 by vein over 2 hours followed by 200 mg/m2 over 22 hours on Day 22.


Drug: Cytarabine

Phase 1A: Cytarabine 100 mg intrathecally on Day 7.

Phase 2A to 4A: Cytarabine 100 mg intrathecally on Day 7.

Phase 1B to 4B: Cytarabine 0.5 g/m2by vein every 12 hours for 4 doses on Days 23 and 24.

Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride

Drug: Rituximab

Phase 1A: For patients with CD20 expression (≥20% by flow cytometry), Rituximab 375 mg/m2 may be added at the discretion of the treating physician. Recommended days of Rituximab administration are Days -3 and 0 (prior to initiation of blinatumomab).

Phase 2A to 4A: For patients with CD20 expression (≥20% by flow cytometry), Rituximab 375 mg/m2 may be added at the discretion of the treating physician. Recommended days of Rituximab administration are Days 1 and 8.

Phase 1B to 4B: • For patients with CD20 expression (≥20% by flow cytometry), Rituximab 375 mg/m2 may be added at the discretion of the treating physician. Recommended days of Rituximab administration are Days 22 and 29.

Other Name: Rituxan

Drug: Blinatumomab

Participants receive Blinatumomab as continuous intravenous infusion over 4 weeks followed by a treatment-free period of 2 weeks, defined as one 42-day treatment cycle. A total of 4 cycles of Blinatumomab are planned for induction/consolidation and 2 cycles during maintenance.

Cycles 2 to 4: Blinatumomab given at a dose of 28 ug/day on Days 1 through Day 29.





Primary Outcome Measures :
  1. Event Free Survival (EFS) [ Time Frame: 2 years ]
    Event free survival (EFS) defined as no response, loss of response, or death.


Secondary Outcome Measures :
  1. Relapse-Free Survival [ Time Frame: 2 years ]
    Relapse-free survival is the time from documented complete response until relapse or death.

  2. Overall Response Rate [ Time Frame: 2 years ]
    Overall response rate defined as the percentage of patients achieving CR or CRi

  3. Overall Survival [ Time Frame: 2 years ]
    Overall survival defined as the time from the first day of treatment to time of death from any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03518112


Contacts
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Contact: Elias Jabbour, MD 713-792-4764 ejabbour@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77339
Contact       ejabbour@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Amgen
Investigators
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Principal Investigator: Elias Jabbour, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03518112     History of Changes
Other Study ID Numbers: 2017-0127
NCI-2018-00737 ( Registry Identifier: NCI CTRP )
First Posted: May 8, 2018    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
Rituximab
Methotrexate
Cytarabine
Vincristine
Blinatumomab
BB 1101
Lenograstim
Antibodies, Bispecific
Mesna
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs