LeukemiaPhase 2NCT01319981
Hyper-CVAD With Liposomal Vincristine in Acute Lymphoblastic Leukemia
A Phase 2 study testing Rituximab, Imatinib and Cyclophosphamide in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- Rituximab, Imatinib and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Mar 2013to 11 Nov 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed previously untreated ALL or lymphoblastic lymphoma >/= 18 years old. Allow urgent administration of cytarabine/hydrea/atra prior to starting treatment on protocol. Allow previous administration of up to one course of Hyper-CVAD and/or FDA approved TKI.
- Zubrod performance status </= 3.
- Adequate liver function (bilirubin </= 3.0 mg/dl unless considered due to tumor) and renal function (creatinine </= 3.0 mg/dl, unless considered due to tumor).
- No active co-existing malignancy with life expectancy less than 12 months due to that malignancy.
- All men and women of childbearing potential who are participating in the study must agree to use effective forms of birth control throughout the duration of their treatment.
- Adequate cardiac function as assessed clinically
Who cannot join
- Pregnant or lactating women. Women of childbearing potential (WOCB) must have a blood or urine pregnancy test within 7 days prior to administration of the study drug. (WOCB is defined as a woman who has not undergone hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months).
- Active Grade III-IV cardiac failure as defined by the New York Heart Association criteria, uncontrolled angina or MI within 6 months.
- Patients with medical conditions that compromise their ability to complete the study or confound interpretation of study results.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Hyper-CVAD With Liposomal Vincristine (Hyper-CMAD) in Acute Lymphoblastic Leukemia
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.
Read more
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.
Read the detailed 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.
- Conditions
- Leukemia
- Being tested
- Rituximab, Imatinib, Cyclophosphamide, Doxorubicin, Mesna
- Keywords
- Acute Lymphoblastic Leukemia, ALL, Lymphoblastic lymphoma, Cytoxan, Neosar, Mesnex, Liposomal Vincristine, Vincristine Sulfate Liposomes Injection, Marqibo, Dexamethasone, Adriamycin, Rubex, Cytarabine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride, Imatinib Mesylate, Gleevec, ST1571, NSC-716051
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
In CD20-positive patients, 375 mg/m2 by vein on day 1 and 8 for Courses 1 and 3; and day 1 and 8 of Courses 2 and 4.
ImatinibDrug
Also called Imatinib Mesylate, Gleevec, ST1571, NSC-716051
600 mg by mouth daily days 1-14 for course 1 and continuously on all other courses for patients who are Philadelphia chromosome positive (Ph+).
CyclophosphamideDrug
Also called Cytoxan, Neosar
300 mg/m2 by vein over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2) for courses 1, 3, 5, 7
DoxorubicinDrug
Also called Adriamycin, Rubex
50 mg/m2 by vein over 24 hours on day 4 after last dose of Cyclophosphamide for courses 1, 3, 5, 7
MesnaDrug
Also called Mesnex
600 mg/m2 by vein continuous infusion daily for 24 hours days 1-3 for courses 1, 3, 5, 7
VSLIDrug
Also called Liposomal Vincristine, Vincristine Sulfate Liposomes Injection, Marqibo
2.0 mg/m2 by vein on day 1 and day 8 for courses 1, 3, 5, 7
Solu-MedrolDrug
Also called Methylprednisolone, Depo-Medrol, Medrol
40 mg by vein every 12 hours for 6 doses days 1-3 for courses 2, 4, 6, 8.
MethotrexateDrug
200 mg/m2 IV over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 beginning after the completion of rituximab for Courses 2, 4, 6, and 8.
Ara-CDrug
Also called Cytarabine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
3 gm/m2 by vein over 2 hours every 12 hours for 4 doses on days 2, 3 for Courses 2, 4, 6, and 8.
G-CSFDrug
Also called Filgrastim, Neupogen
10 µg/kg/day (rounded) given subcutaneously until neutrophil recovery to 1 x 10^9/L or higher can be substituted or can be added if neutrophils have not recovered to 1 x 10^9/L by day 21.
PegfilgrastimDrug
Also called Neulasta
6 mg/kg (rounded) within 72 hrs after completion of chemotherapy.
DexamethasoneDrug
Also called Decadron
40 mg by vein or by mouth daily days 1-4 and days 11-14 for courses 1, 3, 5, 7
| Study group | Role | What they receive |
|---|---|---|
| Hyper-CMAD + Rituximab | Experimental | Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 \& 8 Courses 1 \& 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 \& 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days. Receives: Drug: Rituximab; Drug: Imatinib; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Mesna; Drug: VSLI; Drug: G-CSF; Drug: Pegfilgrastim; Drug: Dexamethasone |
| Hyper-CMAD | Experimental | Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 \& 8 Courses 2 \& 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day. Receives: Drug: Rituximab; Drug: Imatinib; Drug: VSLI; Drug: Solu-Medrol; Drug: Methotrexate; Drug: Ara-C; Drug: G-CSF; Drug: Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Complete Remission at One Year
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of </=5% blasts in the bone marrow, with >1x10^9/L neutrophils, >100x10^9/L platelets in the perpherial blood, and no extramedullary disease.
Measured: 1 year
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.
Measured: Up to 7 years, 8 months
Complete Response Duration
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of </=5% blasts in the bone marrow, with >1x10^9/L neutrophils, >100x10^9/L platelets in the perpherial blood, and no extramedullary disease. Response date to loss of response or last follow up. Remission duration will be measured by the estimated median remission duration computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative remission duration drops below 50%, if present. If not present then median remission duration is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis..
Measured: Up to 7 years, 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2011 (estimated)
- Study start5 Mar 2013
- Primary completion11 Nov 2020
- Study completion11 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Spectrum Pharmaceuticals, Inc
- Responsible party
- Sponsor
- Investigators
- Elias Jabbour, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319981
- Sponsor's protocol ID
- 2008-0598
- Other IDs
- NCI-2011-00861
- Status last verified
- Aug 2022
- First submitted
- 18 Mar 2011
- Last updated
- 27 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyper-CVAD With Liposomal Vincristine (Hyper-CMAD) in Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT01319981
- Acronym / sponsor ID
- 2008-0598
- Conditions
- Leukemia
- Keywords
- Acute Lymphoblastic Leukemia, ALL, Lymphoblastic lymphoma, Cytoxan, Neosar, Mesnex, Liposomal Vincristine, Vincristine Sulfate Liposomes Injection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Spectrum Pharmaceuticals, Inc
- Study start
- 5 Mar 2013 (actual)
- Primary completion
- 11 Nov 2020 (actual)
- Study completion
- 11 Nov 2020 (actual)
- First posted
- 22 Mar 2011 (estimated)
- Results
- Posted 27 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hyper-CMAD + Rituximab | Experimental | Drug: Rituximab, Drug: Imatinib, Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: Mesna, Drug: VSLI, Drug: G-CSF, Drug: Pegfilgrastim, Drug: DexamethasoneOdd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 \& 8 Courses 1 \& 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 \& 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days. |
| Hyper-CMAD | Experimental | Drug: Rituximab, Drug: Imatinib, Drug: VSLI, Drug: Solu-Medrol, Drug: Methotrexate, Drug: Ara-C, Drug: G-CSF, Drug: PegfilgrastimCourses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 \& 8 Courses 2 \& 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Newly diagnosed previously untreated ALL or lymphoblastic lymphoma >/= 18 years old. Allow urgent administration of cytarabine/hydrea/atra prior to starting treatment on protocol. Allow previous administration of up to one course of Hyper-CVAD and/or FDA approved TKI.
- Zubrod performance status </= 3.
- Adequate liver function (bilirubin </= 3.0 mg/dl unless considered due to tumor) and renal function (creatinine </= 3.0 mg/dl, unless considered due to tumor).
- No active co-existing malignancy with life expectancy less than 12 months due to that malignancy.
- All men and women of childbearing potential who are participating in the study must agree to use effective forms of birth control throughout the duration of their treatment.
Key exclusion criteria (3 listed)
- Pregnant or lactating women. Women of childbearing potential (WOCB) must have a blood or urine pregnancy test within 7 days prior to administration of the study drug. (WOCB is defined as a woman who has not undergone hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months).
- Active Grade III-IV cardiac failure as defined by the New York Heart Association criteria, uncontrolled angina or MI within 6 months.
- Patients with medical conditions that compromise their ability to complete the study or confound interpretation of study results.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: RituxanIn CD20-positive patients, 375 mg/m2 by vein on day 1 and 8 for Courses 1 and 3; and day 1 and 8 of Courses 2 and 4. | Drug | Hyper-CMAD, Hyper-CMAD + Rituximab |
| ImatinibAlso: Imatinib Mesylate, Gleevec, ST1571, NSC-716051600 mg by mouth daily days 1-14 for course 1 and continuously on all other courses for patients who are Philadelphia chromosome positive (Ph+). | Drug | Hyper-CMAD, Hyper-CMAD + Rituximab |
| CyclophosphamideAlso: Cytoxan, Neosar300 mg/m2 by vein over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2) for courses 1, 3, 5, 7 | Drug | Hyper-CMAD + Rituximab |
| DoxorubicinAlso: Adriamycin, Rubex50 mg/m2 by vein over 24 hours on day 4 after last dose of Cyclophosphamide for courses 1, 3, 5, 7 | Drug | Hyper-CMAD + Rituximab |
| MesnaAlso: Mesnex600 mg/m2 by vein continuous infusion daily for 24 hours days 1-3 for courses 1, 3, 5, 7 | Drug | Hyper-CMAD + Rituximab |
| VSLIAlso: Liposomal Vincristine, Vincristine Sulfate Liposomes Injection, Marqibo2.0 mg/m2 by vein on day 1 and day 8 for courses 1, 3, 5, 7 | Drug | Hyper-CMAD, Hyper-CMAD + Rituximab |
| Solu-MedrolAlso: Methylprednisolone, Depo-Medrol, Medrol40 mg by vein every 12 hours for 6 doses days 1-3 for courses 2, 4, 6, 8. | Drug | Hyper-CMAD |
| Methotrexate200 mg/m2 IV over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 beginning after the completion of rituximab for Courses 2, 4, 6, and 8. | Drug | Hyper-CMAD |
| Ara-CAlso: Cytarabine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride3 gm/m2 by vein over 2 hours every 12 hours for 4 doses on days 2, 3 for Courses 2, 4, 6, and 8. | Drug | Hyper-CMAD |
| G-CSFAlso: Filgrastim, Neupogen10 µg/kg/day (rounded) given subcutaneously until neutrophil recovery to 1 x 10^9/L or higher can be substituted or can be added if neutrophils have not recovered to 1 x 10^9/L by day 21. | Drug | Hyper-CMAD, Hyper-CMAD + Rituximab |
| PegfilgrastimAlso: Neulasta6 mg/kg (rounded) within 72 hrs after completion of chemotherapy. | Drug | Hyper-CMAD, Hyper-CMAD + Rituximab |
| DexamethasoneAlso: Decadron40 mg by vein or by mouth daily days 1-4 and days 11-14 for courses 1, 3, 5, 7 | Drug | Hyper-CMAD + Rituximab |
Primary outcome
Number of Patients With Complete Remission at One Year
Time frame: 1 year
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of </=5% blasts in the bone marrow, with >1x10^9/L neutrophils, >100x10^9/L platelets in the perpherial blood, and no extramedullary disease.
Overall Survival
Time frame: Up to 7 years, 8 months
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.
Complete Response Duration
Time frame: Up to 7 years, 8 months
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of </=5% blasts in the bone marrow, with >1x10^9/L neutrophils, >100x10^9/L platelets in the perpherial blood, and no extramedullary disease. Response date to loss of response or last follow up. Remission duration will be measured by the estimated median remission duration computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative remission duration drops below 50%, if present. If not present then median remission duration is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis..
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elias Jabbour, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, Imatinib and Cyclophosphamide in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Complete Remission at One Year (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022; AzTrials last refreshed its copy on 6 Nov 2026.