Efficacy of the HCVIDDOXIL Regimen in Patients With Newly Diagnosed Peripheral T-Cell Lymphoma

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00290433
Collaborator
Ortho Biotech, Inc. (Industry)
55
1
1
142
0.4

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if treatment with two types of chemotherapy combinations can help to control peripheral T-cell lymphoma.

Detailed Description

All of the drugs used in this study are commonly used in the treatment of cancer. However, using these drugs in combination is investigational.

During treatment, you will be given two different cycles of chemotherapy, which will be alternated every 21 days.

For Cycle 1, cyclophosphamide will be given by vein two times a day on Days 1,2, and 3. Each dose will take around 3 hours to give. Mesna will be given by vein nonstop over Days 1 through 3. Pegylated liposomal doxorubicin will be given by vein over 1 hour on Day 2. Vincristine will be given by vein on Days 4 and 11. Dexamethasone will be given by mouth on Days 1 through 4 and 11 through 14. Other drugs will be given before, during, and after chemotherapy to help decrease the risk of developing side effects. These drugs may be given by mouth or by injection.

For Cycle 2, methotrexate will be given by vein over 2 hours on Day 1 and over 22 hours on day 1. Cytarabine will be given by vein twice a day on Days 2 and 3. Each dose will take about 2 hours to give. Other drugs will be given before, during, and after treatment to help decrease the risk of developing side effects. These drugs may be given by mouth or by injection.

To help increase the blood counts and help decrease the risk of developing infections, your doctor may decide that treatment with filgrastim is necessary. Filgrastim may be given as once-a-day injections under the skin starting 24 hours after the end of Day 4 vincristine (Cycle 1) and starting 24 hours after the end of Cytarabine (Cycle 2). Your blood counts will be monitored and filgrastim is stopped when the levels become normal.

Cycles 1 and 2 will be alternated every 21 days. Both Cycles 1 and 2 can be given on an outpatient basis if your physician authorizes it. However, if your serum creatinine (blood test) reaches a certain level, Cycle 2 should be given on an inpatient basis.

Depending on how the disease responds, treatment may be stopped after 2,4, or 6 cycles. However, treatment may continue for up to 8 cycles.

During treatment, you will have around 2-3 tablespoons of blood collected at least once a week for routine tests.

After every 2 cycles, tumors will be measured using x-rays or other scans (CT, MRI, etc.) and bone marrow samples will be taken. Heart scans or heart function tests may also be needed if you doctor feels it is necessary.

If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

After the last cycle of chemotherapy, you will have follow-up exams scheduled. During these exams, you will have a chest x-ray and CT scans of the chest, abdomen (stomach) and pelvis (waist area), and PET scan. You will have blood collected (2-3 tablespoons) for routine tests. If your doctor feels it is necessary, you may also have a sample of bone marrow collected. You may choose to have long-term follow-up exams at M. D. Anderson or with your local physician.

This is an investigational study. All of the study drugs are approved by the FDA for cancer treatment and are commercially available. However, the use of the drugs in combination is experimental. Up to 55 participants will take part in this study. All will be enrolled at M.

  1. Anderson.

Study Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of the Efficacy of the HCVIDDOXIL Regimen in Patients With Newly Diagnosed Peripheral T Cell Lymphoma
Study Start Date :
Sep 1, 2003
Actual Primary Completion Date :
Jul 1, 2015
Actual Study Completion Date :
Jul 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: HCVIDDOXIL Regimen

Cycle 1: Cyclophosphamide by vein two times a day on Days 1,2, and 3. Mesna by vein nonstop over Days 1 through 3. Pegylated liposomal doxorubicin by vein over 1 hour on Day 2. Vincristine by vein on Days 4 and 11. Dexamethasone by mouth on Days 1 through 4 and 11 through 14. Cycle 2: Methotrexate by vein over 2 hours on Day 1 and over 22 hours on day 1. Cytarabine by vein twice a day on Days 2 and 3.

Drug: Cyclophosphamide
Cycle 1: 300 mg/m^2 by vein Over 3 Hours Twice Daily on Days 1, 2, and 3.
Other Names:
  • Cytoxan
  • Neosar
  • Drug: Mesna
    Cycle 1: 600 mg/m^2 by vein Continuous Infusion Over Days 1, 2, and 3.

    Drug: Vincristine
    Cycle 1: 1.4 mg/m^2 by vein On Day 4 and 11.

    Drug: Methotrexate
    Cycle 1 and 2: 200 mg/m^2 by vein Over 2 Hours on Day 1, followed by 800 mg/m^2 IV Over 22 Hours on Day 1.

    Drug: Ara-C
    Cycle 1 and 2: 3 Gm/m^2 Over 2 Hours Twice Daily On Days 2 and 3.
    Other Names:
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Drug: Dexamethasone
    Cycle 1: 40 mg by vein or by mouth daily on Days 1-4 and 11-14.
    Other Names:
  • Decadron
  • Drug: G-CSF
    Cycle 1 and 2: 300 or 480 mcg subcutaneously 24 hours after end of Day 4 vincristine.
    Other Names:
  • Filgrastim
  • Neupogen
  • Drug: Doxil
    Cycle 1: 25 mg/m^2 by vein Over 1 Hour on Day 2.
    Other Names:
  • Pegylated Liposomal Doxorubicin
  • Doxorubicin hydrochloride (lipsomal)
  • Outcome Measures

    Primary Outcome Measures

    1. 3 Year Progression-Free Survival Rate [From registration to disease progression or death, up to 3 years]

      Percentage of participants out of total treated alive with disease progression 3 years following registration. Progression-free survival (PFS) was measured from the date of study registration to the date of documented disease progression or death of any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Confirmed diagnosis of previously untreated T-cell Non Hodgkin's Lymphomas and NK lymphomas, with the exception of cluster of differentiation antigen 30 (CD30+) alk1+ T-anaplastic large cell lymphoma (ALCL). Patients with skin involvement alone are also excluded. For patients with skin involvement as part of systemic disease, prior topical treatment only is allowed.

    2. Patients with a performance status of 3 or less (Zubrod Scale - see Appendix D).

    3. Serum bilirubin </= 1.5 mg/dl and serum creatinine </= 2.0 mg/dl unless due to lymphoma; Absolute neutrophil count (ANC) >/= 1000 mm3 and platelets >/= 100,000 mm3 unless due to lymphoma.

    4. Cardiac ejection fraction 50% or greater by multigated radionuclide angiography (MUGA) or echocardiogram.

    5. Ages 18 and older.

    6. Patients must be willing to receive transfusions of blood products.

    Exclusion Criteria:
    1. Patients with CD30+ alk1+ T-anaplastic large cell lymphoma (ALCL) or patients with skin involvement alone.

    2. Pregnancy

    3. HIV positive serology

    4. Central nervous system (CNS) involvement

    5. Co-morbid medical, such as Child's Class C liver cirrhosis, end-stage renal disease, and symptomatic congestive heart failure, or psychiatric illnesses that preclude treatment with intense dose chemotherapy as determined by the primary investigator

    6. Concurrent or previous malignancy whose prognosis is poor (<90% probability of survival at 5 years)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • Ortho Biotech, Inc.

    Investigators

    • Principal Investigator: Yasuhiro Oki, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00290433
    Other Study ID Numbers:
    • ID03-0004
    • NCI-2010-00445
    First Posted:
    Feb 13, 2006
    Last Update Posted:
    Sep 23, 2020
    Last Verified:
    Sep 1, 2020

    Study Results

    Participant Flow

    Recruitment Details Recruitment period: September 17, 2003 to May 8, 2009. All recruitment done at The University of Texas MD Anderson Cancer Center.
    Pre-assignment Detail Of the 55 participants registered, two participants were found not to be eligible prior to start of study therefore are excluded from trial details.
    Arm/Group Title HCVIDDOXIL Regimen
    Arm/Group Description Cycle 1: Cyclophosphamide 300 mg/m^2 intravenous (IV) twice a day on Days 1-3. Mesna 600 mg/m^2 continuous IV Days 1-3. Doxil 25 mg/m^2 IV over 1 hour on Day 2. Vincristine 1.4 mg/m^2 IV on Days 4 and 11. Dexamethasone 40 mg Iv or oral on Days 1 - 4 and 11 - 14. Cycle 2: Methotrexate 200 mg/m^2 over 2 hours on Day 1 and 800 mg/m^2 over 22 hours on day 1. Cytarabine 3 Gm/m^2 IV twice a day on Days 2 and 3.
    Period Title: Overall Study
    STARTED 53
    COMPLETED 17
    NOT COMPLETED 36

    Baseline Characteristics

    Arm/Group Title HCVIDDOXIL Regimen
    Arm/Group Description Cycle 1: Cyclophosphamide 300 mg/m^2 intravenous (IV) twice a day on Days 1-3. Mesna 600 mg/m^2 continuous IV Days 1-3. Doxil 25 mg/m^2 IV over 1 hour on Day 2. Vincristine 1.4 mg/m^2 IV on Days 4 and 11. Dexamethasone 40 mg Iv or oral on Days 1 - 4 and 11 - 14. Cycle 2: Methotrexate 200 mg/m^2 over 2 hours on Day 1 and 800 mg/m^2 over 22 hours on day 1. Cytarabine 3 Gm/m^2 IV twice a day on Days 2 and 3.
    Overall Participants 53
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    54
    Sex: Female, Male (Count of Participants)
    Female
    26
    49.1%
    Male
    27
    50.9%
    Region of Enrollment (participants) [Number]
    United States
    53
    100%

    Outcome Measures

    1. Primary Outcome
    Title 3 Year Progression-Free Survival Rate
    Description Percentage of participants out of total treated alive with disease progression 3 years following registration. Progression-free survival (PFS) was measured from the date of study registration to the date of documented disease progression or death of any cause.
    Time Frame From registration to disease progression or death, up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Of the 53 participants, *6 participants* were not evaluable for response due to either no measurable disease (1) or early departure from study for adverse events (5)
    Arm/Group Title HCVIDDOXIL Regimen
    Arm/Group Description Cycle 1: Cyclophosphamide 300 mg/m^2 intravenous (IV) twice a day on Days 1-3. Mesna 600 mg/m^2 continuous IV Days 1-3. Doxil 25 mg/m^2 IV over 1 hour on Day 2. Vincristine 1.4 mg/m^2 IV on Days 4 and 11. Dexamethasone 40 mg Iv or oral on Days 1 - 4 and 11 - 14. Cycle 2: Methotrexate 200 mg/m^2 over 2 hours on Day 1 and 800 mg/m^2 over 22 hours on day 1. Cytarabine 3 Gm/m^2 IV twice a day on Days 2 and 3.
    Measure Participants 47
    Number (95% Confidence Interval) [percentage of participants]
    30
    56.6%

    Adverse Events

    Time Frame Adverse events were assessed from the initiation of the regimen through the end of the chemotherapy cycle, up to 3 years.
    Adverse Event Reporting Description
    Arm/Group Title HCVIDDOXIL Regimen
    Arm/Group Description Cycle 1: Cyclophosphamide 300 mg/m^2 intravenous (IV) twice a day on Days 1-3. Mesna 600 mg/m^2 continuous IV Days 1-3. Doxil 25 mg/m^2 IV over 1 hour on Day 2. Vincristine 1.4 mg/m^2 IV on Days 4 and 11. Dexamethasone 40 mg Iv or oral on Days 1 - 4 and 11 - 14. Cycle 2: Methotrexate 200 mg/m^2 over 2 hours on Day 1 and 800 mg/m^2 over 22 hours on day 1. Cytarabine 3 Gm/m^2 IV twice a day on Days 2 and 3.
    All Cause Mortality
    HCVIDDOXIL Regimen
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    HCVIDDOXIL Regimen
    Affected / at Risk (%) # Events
    Total 1/53 (1.9%)
    Infections and infestations
    massive cytomegalovirus infection 1/53 (1.9%) 1
    Other (Not Including Serious) Adverse Events
    HCVIDDOXIL Regimen
    Affected / at Risk (%) # Events
    Total 46/53 (86.8%)
    Blood and lymphatic system disorders
    Neutropenia 42/53 (79.2%) 42
    Anemia 46/53 (86.8%) 46
    Thrombocytopenia 46/53 (86.8%) 46
    Febrile Neutropenia 21/53 (39.6%) 21
    Gastrointestinal disorders
    Constipation 19/53 (35.8%) 19
    General disorders
    Fever 35/53 (66%) 35
    Fatigue 40/53 (75.5%) 40
    Edema 36/53 (67.9%) 36
    Hepatobiliary disorders
    Liver Toxicities 21/53 (39.6%) 21
    Infections and infestations
    Infectious Disease 19/53 (35.8%) 19
    Metabolism and nutrition disorders
    Hyperglycemia 11/53 (20.8%) 11
    Nervous system disorders
    Dizziness 19/53 (35.8%) 19
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 19/53 (35.8%) 19
    Mucositis 16/53 (30.2%) 16
    Skin and subcutaneous tissue disorders
    Rash 10/53 (18.9%) 10

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Christopher Flowers/Chair, Lymphoma-Myeloma
    Organization The University of Texas (UT) MD Anderson Cancer Center
    Phone 713-745-6095
    Email crflowers@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00290433
    Other Study ID Numbers:
    • ID03-0004
    • NCI-2010-00445
    First Posted:
    Feb 13, 2006
    Last Update Posted:
    Sep 23, 2020
    Last Verified:
    Sep 1, 2020