Clinical Trials /

Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

NCT01363128

Description:

This phase II trial studies how well combination chemotherapy and ofatumumab work in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with ofatumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy together with ofatumumab may be an effective treatment for acute lymphoblastic leukemia or lymphoblastic lymphoma.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Burkitt Leukemia
  • Burkitt Lymphoma
  • Lymphoblastic Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hyper CVAD Plus Ofatumumab in CD - 20 Positive Acute Lymphoblastic Leukemia (ALL)
  • Official Title: Phase II Study of the Hyper - CVAD Regimen in Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2010-0708
  • SECONDARY ID: NCI-2011-01061
  • NCT ID: NCT01363128

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
CyclophosphamideCytoxan, NeosarHyper-CVAD + Ofatumumab
MesnaMesnexHyper-CVAD + Ofatumumab
DoxorubicinAdriamycin, RubexHyper-CVAD + Ofatumumab
VincristineHyper-CVAD + Ofatumumab
DexamethasoneDecadronHyper-CVAD + Ofatumumab
OfatumumabArzerraHyper-CVAD + Ofatumumab
MethotrexateHyper-CVAD + Ofatumumab
CytarabineAra-C, Cytosar, DepoCyt, Cytosine Arabinosine HydrochlorideHyper-CVAD + Ofatumumab

Purpose

The goal of this clinical research study is to learn if ofatumumab combined with standard chemotherapy can help to control ALL. The safety of these drug combinations will also be studied.

Detailed Description

Study Drug:

Ofatumumab is designed to bind to the surface of a type of white blood cells. This may cause cancer cells that come from these white blood cells to die.

Central Venous Catheter (CVC):

If you are found to be eligible to take part in this study, you will receive a 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.

Study Plan:

During Cycles 1-8, you will receive ofatumumab during Cycles 1, 2, 3, and 4. During Cycles 1, 3, 5, and 7, you also will receive cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD). During Cycles 2, 4, 6, and 8, you will also receive methotrexate and cytarabine.

After Cycles 1-8, you will receive up to 30 cycles of Maintenance therapy.

During Maintenance:

- During Cycles 1-5, 8-17, and 20-30, you will receive 6-mercaptopurine, methotrexate, vincristine, and prednisone.

- During Cycles 6 and 18 (or Cycles 7 and 19), you will receive cyclophosphamide, vincristine, doxorubicin, dexamethasone, and ofatumumab.

- During Cycles 7 and 19 (or Cycles 6 and 18), you will receive methotrexate and pegaspargase.

First Phase of Treatment (Cycles 1-8):

Every 21 days is a study cycle.

You will receive ofatumumab by vein over 4-6 hours on Days 1 and 11 of Cycles 1 and 3 and on Days 1 and 8 of Cycles 2 and 4.

During Cycles 1, 3, 5, and 7, you will also receive the following drugs:

- On Days 1-3, you will receive cyclophosphamide 2 times a day by vein over 3 hours.

- On Days 1-3, you will receive mesna by vein non-stop for the 3 days. The mesna infusion will end about 12 hours after the last dose of cyclophosphamide.

- On Day 4, you will receive doxorubicin by vein non-stop for 1 day through the CVC.

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

- On Days 1-4 and 11-14, you will receive dexamethasone 1 time a day by vein over 30 minutes or by mouth.

During Cycles 2, 4, 6, and 8, you will also receive the following drugs:

- On Day 1, you will receive methotrexate by vein over 24 hours. If your doctor thinks it is needed to help reduce the risk of side effects, you may receive leucovorin by vein 4 times a day for 8 doses, beginning 12 hours after the Day 1 methotrexate dose ends.

- On Days 2 and 3, you will receive cytarabine by vein 2 times a day over 2 hours.

You may receive filgrastim or pegfilgrastim at the end of every cycle to help raise your blood cell counts after you finish chemotherapy. If you receive filgrastim, it will be given by a needle under your skin. If you receive pegfilgrastim, it will be given by a needle under your skin.

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.

If you are previously untreated for cancer, you will receive the following drugs during Cycles 1-4, or Cycles 1-8 if you have Burkitt's Leukemia/Lymphoma, to help prevent disease in your brain and spinal fluid:

- On Day 2, you will receive methotrexate as an injection into the spinal canal (the space surrounding the spinal cord).

- On Day 7, you will receive cytarabine as an injection into the spinal canal.

If you have mediastinal lymphoblastic lymphoma and bulky mediastinal disease or mediastinal lymphadenopathy (enlarged lymph nodes in the chest area), you may have radiation therapy to the chest area based on the status of the disease. The radiation therapy will be given after you recover from Cycle 8 and before you start Maintenance therapy. Your doctor will explain radiation therapy to you in more detail, and you will be required to sign a separate consent form for this procedure.

Maintenance Therapy:

During Maintenance Cycles 1-5, 8-17, and 20-30:

- You will take 6-mercaptopurine by mouth 3 times daily.

- On Day 1, you will receive vincristine by vein over 15 minutes.

- You will take methotrexate by mouth weekly.

- On Days 1-5, you will take prednisone by mouth.

During Maintenance Cycles 6 and 18 (or Cycles 7 and 19), you will receive the same drugs on the same schedule as you did during Cycles 1 and 3.

During Maintenance Cycles 7 and 19 (or Cycles 6 and 18):

- You will receive methotrexate on Day 1 by vein over 2 hours.

- You will receive pegaspargase on Day 2 by vein over 2 hours.

If you have Burkitt Leukemia/Lymphoma, you will only receive induction, consolidation and intrathecal chemotherapy (injected into the spinal canal). You will not receive maintenance therapy.

Study Visits:

You will have a physical exam before each cycle.

One (1) time a week during Cycles 1-8, then 1 time a month during Maintenance, blood (about 2-3 teaspoons) will be drawn for routine tests.

On Day 14 of Cycle 1, then 1 time a week, you will have a bone marrow aspiration and/or biopsy to check the status of the disease. If the cancer goes into remission (no sign of disease) the bone marrow aspirations/biopsies will then be performed every 4 months.

You will have a chest x-ray or PET/CT scan anytime the doctor thinks it is needed.

Length of Study:

You may receive up to 38 cycles of study drugs. 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.

Follow-Up:

You will be followed for side effects until 30 days after your last dose of study drugs. You will have blood (about 2-3 teaspoons) drawn.

Long-Term Follow-Up:

The study staff will call you every 3 months for 1 year after you finish receiving the study drugs. During the calls, you will be asked how are you feeling and about any side effects you may have had and any drugs you may have taken.

This is an investigational study. Ofatumumab is FDA approved or commercially available for the treatment of chronic lymphocytic leukemia. Its use to treat ALL is investigational.

Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.

Trial Arms

NameTypeDescriptionInterventions
Hyper-CVAD + OfatumumabExperimentalHyper-CVAD + Ofatumumab (odd courses) Hyper-CVAD + High Dose Methotrexate + Cytarabine + Ofatumumab (even courses)
  • Cyclophosphamide
  • Mesna
  • Doxorubicin
  • Vincristine
  • Dexamethasone
  • Ofatumumab
  • Methotrexate
  • Cytarabine

Eligibility Criteria

Inclusion Criteria:

1. Patients of all ages with newly diagnosed, previously untreated CD-20+ ALL, or lymphoblastic lymphoma, Burkitt Leukemia/Lymphoma or having achieved CR with one course of induction chemotherapy.

2. Failure to one induction course of chemotherapy (these patients will be analyzed separately).

3. Performance status of 0, 1, or 2.

4. Adequate organ function with creatinine less than or equal to 3.0 mg/dL (unless considered tumor related), bilirubin less than or equal to 3.0 mg/dL (unless considered tumor related).

5. Adequate cardiac function defined as no clinically significant history of arrhythmia as determined by the PI and/or the treating physician, history of MI or clinically significant abnormal EKG, as determined by the PI and/or the treating physician, within 3 months prior to study enrollment. Cardiac function will be assessed by history and physical examination.

6. No active or co-existing malignancy(other than ALL or lymphoblastic lymphoma) with life expectancy less than 12 months due to that malignancy.

Exclusion Criteria:

1. Pregnant or nursing women.

2. Known to be HIV+

3. Ph+ ALL

4. Active and uncontrolled disease/infection as judged by the treating physician

5. Unable or unwilling to sign the consent form

6. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)

7. Treatment with any known non - marketed drug substance or experimental therapy within 5 terminal half lives (calculated by multiplying the reported terminal half life by 5) or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study.

8. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae

9. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. Consult with a physician experienced in care & management of subjects with hepatitis B to manage/treat subjects who are anti-HBc positive.

10. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result.

Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event-Free Survival (EFS)
Time Frame:Assessed beginning Day 14 of Cycle 1, on-going to disease progression (estimated 3+ years)
Safety Issue:
Description:Event-free survival measured from the start of therapy until failure to respond, relapse or death.

Secondary Outcome Measures

Details

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

Trial Keywords

  • Leukemia
  • Acute Lymphoblastic Leukemia
  • CD-20 Positive Acute Lymphoblastic Leukemia
  • Any level of CD20 expression
  • Lymphoblastic lymphoma
  • Central Venous Catheter
  • CVC
  • HCVAD
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Mesna
  • Mesnex
  • Doxorubicin
  • Adriamycin
  • Rubex
  • Vincristine
  • Dexamethasone
  • Decadron
  • Ofatumumab
  • Arzerra
  • Methotrexate
  • Cytarabine
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

Last Updated

September 12, 2016