Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01319981 |
| Other study ID # |
2008-0598 |
| Secondary ID |
NCI-2011-00861 |
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 5, 2013 |
| Est. completion date |
November 11, 2020 |
Study information
| Verified date |
August 2022 |
| Source |
M.D. Anderson Cancer Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential
participant.
The goal of this clinical research study is to learn if intensive chemotherapy (hyper-CVAD
therapy) given in combination with liposomal vincristine (Marqibo), in addition to rituximab
for patients who are CD20 positive and/or imatinib, dasatinib, or ruxolitinib for patients
with the Philadelphia (Ph) chromosome, can help to control ALL or lymphoblastic lymphoma. The
safety of this treatment will also be studied. CD20 is a protein "marker" that is found in
leukemia or lymphoma cells.
This is an investigational study. Liposomal vincristine is FDA approved for the treatment of
patients with CLL who have relapsed at least 2 times. All of the other study drugs used in
this study are FDA approved and commercially available. The combination of liposomal
vincristine with the other study drugs is also being used in research only.
Up to 65 patients will take part in this study. All will be enrolled at MD Anderson.
Description:
The Study Drugs:
Adriamycin (doxorubicin) is designed to stop the growth of cancer cells, which may cause the
cells to die.
Cyclophosphamide is designed to disrupt with the multiplication of cancer cells, which may
slow or stop their growth and spread throughout the body. This may cause the cancer cells to
die.
Cytarabine (Ara-C) is designed to insert itself into DNA (the genetic material of cells) of
cancer cells and stop the DNA from repairing itself.
Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body.
Methotrexate is designed to disrupt cells from making and repairing DNA and "copying"
themselves.
Vincristine is designed to disrupt the multiplication of cancer cells, which may slow or stop
their growth and spread throughout the body. This may cause the cancer cells to die.
Liposomal Vincristine (Marqibo) is designed to help vincristine stay in the bloodstream for a
longer time, more specifically target tumor tissue, and deliver more of the drug to a tumor
site over a longer period of time. This may increase how effective the drug is and lower the
risk of possible side effects in healthy, non-tumor tissue.
Rituximab is a monoclonal antibody that is designed to attach to leukemia cells and activate
a series of events that may cause the cancer cells to die.
Tyrosine Kinase Inhibitors (TKI--Imatinib, Dasatinib, or Ruxolitinib) Imatinib is a drug
designed to block cancer cells from growing and dividing.
Dasatinib and ruxolitinib are designed to block a protein that cancer may need to grow,
survive, or spread.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
groups, based on your already performed diagnostic test for a certain protein, called CD20.
- If you test positive for CD20, you will receive hyper-CVAD therapy plus rituximab.
- If you test negative for CD20, you will receive hyper-CVAD therapy only.
In addition, patients with the Philadelphia chromosome (considered Philadelphia-positive or
Ph+) will receive imatinib or dasatinib in either group. Patients with Philadelphia
chromosome-like disease will receive dasatinib or ruxolitinib. The study doctor will decide
which drug these participants will receive.
Study Drug Administration:
Hyper-CVAD therapy is a combination of 7 chemotherapy drugs: the combination of adriamycin
(doxorubicin), cyclophosphamide, and liposomal vincristine, alternating with the combination
of cytarabine (Ara-C), dexamethasone, methotrexate, and liposomal vincristine. You will
receive the 2 different study drug combinations over 21-28 day "courses." You will begin with
Course A treatment and alternate with the Course B treatment every other course. You will
stay overnight in the hospital for the first 4-5 days of each course.
For Course A of treatment, you will receive cyclophosphamide, liposomal vincristine,
doxorubicin, and dexamethasone.
For Course B of treatment, you will receive methotrexate, cytarabine, and liposomal
vincristine.
Courses of treatment on this study will continue to alternate or switch between the Course A
study drug combination for all odd number courses (3, 5, and 7) and the Course B study drug
combination for all even number courses (4, 6, and 8) for a total of up to 8 courses.
While you are on study, all doses of study drug combinations will be given through a central
venous catheter (CVC). 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.
Course 1:
On Days 1, 2, and 3 you will receive cyclophosphamide by vein over about 24 hours, mesna by
vein continuously over 24 hours, and liposomal vincristine by vein over 1 hour +/- 30 minutes
(Day 1 only). Mesna is given to help prevent blood in the urine, which is sometimes caused by
cyclophosphamide.
On Days 2 and 7, methotrexate then cytarabine will be given by intrathecal (IT) infusion
directly into your spinal fluid to lower the risk of the disease spreading to the brain.
On Day 4, you will receive doxorubicin by vein over 24 hours.
On Day 5 or 6, G-CSF will be injected under the skin to help with the recovery of bone marrow
cells recovery 24 hours after the dose of study drugs.
On Day 8, you will receive liposomal vincristine by vein over 1 hour +/- 30 minutes.
On Days 1-4 and Days 11-14, dexamethasone will be given by mouth with a glass of water or by
vein as a short infusion.
CD20 positive patients only will also receive rituximab by vein over 6 hours, on Days 1 and
8, in addition to receiving all study drugs, as described above. If you are CD20 negative,
you will not receive rituximab.
Ph+ participants will receive imatinib by mouth with breakfast and a large glass of water
(about 8 ounces) or dasatinib by mouth on Days 1-14 during Course 1.
Patients with Philadelphia chromosome-like disease will receive dasatinib 1 time each day or
ruxolitinib 2 times each day on Days 1-14 during Course 1.
Course 2:
On Day 1, you will receive methotrexate by vein over 24 hours.
On Days 2 and 3, you will receive cytarabine by vein over 2 hours every 12 hours for a total
of 4 doses. You will also be given citrovorum factor (leucovorin) by vein or by mouth to help
prevent the possible side effects of methotrexate.
On Day 5 or 6, G-CSF will be injected under the skin to help with bone marrow recovery 24
hours after the dose of study drugs.
On Days 5 and 8, cytarabine then methotrexate will be given by IT infusion to lower the risk
of the disease spreading to the brain.
CD20 positive patients only will also receive rituximab by vein over 4 hours, on Days 1 and
8, in addition to receiving all study drugs, as described above. If you are CD20 negative,
you will not receive rituximab.
Ph+ participants will receive imatinib by mouth with breakfast and a large glass of water
(about 8 ounces) every day during Courses 2-8. Dasatinib will be given by mouth every day
during Courses 2-8.
Patients with Philadelphia chromosome-like disease will receive dasatinib 1 time each day or
ruxolitinib 2 times each day.
Course 1 Study Visits:
- Blood (about 5 teaspoons each time) will be drawn weekly for routine tests.
- During Week 2 and 3 or 4, a bone marrow aspirate will be performed to check the status
of the disease.
- At the end of Course 1, if the study doctor thinks it is needed, a chest X-ray or CT
scan will be performed to check the status of the disease.
If the study doctor thinks it is needed, any of these tests may be repeated at any time while
you are receiving the study drug combination.
Radiation Treatment:
If you have lymphoblastic lymphoma and you have enlarged lymph glands in the chest, you may
receive radiation treatment to the chest after completing 8 courses of therapy and before you
begin maintenance therapy. If you are to receive radiation therapy to the chest, the study
doctor will discuss this procedure and its known risks with you in more detail, and you will
be given a separate consent form to sign.
Maintenance Therapy -- Non-Ph+ Participants
After completing 8 courses of the study drug combinations, you will begin maintenance therapy
for a total of 30 months, and will be interrupted by 2 periods of intensive chemotherapy
consolidation courses.
Every month during maintenance therapy:
- You will take 6-mercaptopurine every day by mouth.
- You will receive methotrexate by vein or mouth 1 time every week.
- You will receive liposomal vincristine by vein over 1 hour +/- 30 minutes on Day 1.
- You will take dexamethasone by mouth on Days 1-5 each month.
First intensive chemotherapy consolidation courses:
- Six (6) months after you begin maintenance therapy, you will receive two months of
intensive chemotherapy courses.
- First, you will receive cyclophosphamide, liposomal vincristine, doxorubicin, and
dexamethasone (similar to Course 1) for Month 6 of therapy.
- About one (1) month later, you will receive methotrexate by vein (at a lower dose than
given during Course 2) on Day 1 and pegylated asparaginase by vein over about 2 hours on
Day 2. You will be given each drug 1 time each week for a total of 4 weeks for Month 7
of therapy.
About eighteen (18) months after you begin maintenance therapy, you will repeat the intensive
chemotherapy courses just described.
Maintenance Therapy -- Ph+ Participants and Participants with Ph-like Disease:
After completing 8 courses of the study drug combinations, you will begin maintenance
chemotherapy plus TKI (imatinib or dasatinib if you have Ph+ disease; or dasatinib or
ruxolitinib if you have Ph-like disease). Maintenance chemotherapy will be given for a total
of 24 months, and will be interrupted by 2 periods of intensive chemotherapy courses and the
TKI at 6 and 13 months from the start of maintenance. You will continue receiving the TKI
every day from that point on, unless intolerable side effects occur.
Every month during maintenance therapy:
- You will take imatinib, dasatinib, or ruxolitinib every day by mouth.
- You will receive liposomal vincristine by vein over 1 hour +/- 30 minutes on Day 1.
- You will take dexamethasone by mouth on Days 1-5 each month.
Intensive chemotherapy consolidation courses:
°At six (6) and eighteen (18) months after you begin maintenance therapy, you will receive
two months of intensive chemotherapy courses. You will receive cyclophosphamide, liposomal
vincristine, doxorubicin, and dexamethasone with the TKI (similar to Course 1). If the
disease is CD20 positive, you may receive rituximab.
Blood Tests:
During maintenance therapy and the intensive consolidation therapy, you will have blood
(about 5 teaspoons) drawn every 4 weeks +/- 4 weeks for routine tests.
After intensive chemotherapy consolidation, for as long as you continue to receive
maintenance therapy, blood (about 5 teaspoons) will be drawn every 4 weeks +/- 4 weeks, until
maintenance therapy is completed:
Additional Tests while on Study:
Every 3-6 months:
- You will have a bone marrow biopsy performed to check the status of the disease.
- If you have mediastinal disease, you will have a chest x-ray or CT scan.
Length of Study:
You will receive up to 8 courses of therapy. If you are not Ph+, you will continue to receive
maintenance therapy for up to 30 months. If you are Ph+, you will continue to receive
maintenance therapy for up to 24 months, followed by imatinib or dasatinib alone
indefinitely. You will be taken off the study if disease gets worse, you experience
intolerable side effects, or the study doctor thinks it is in your best interest.
Additional Information:
If you are 60 years or older, you will receive Course 1 chemotherapy in a protective
isolation room to decrease the risk of any infection(s) that you may be exposed to while
receiving the Course 1 treatment.
