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Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Lymphoma

Intervention: Gemcitabine (Drug); Clofarabine (Drug); Busulfan (Drug); Stem Cell Infusion (Procedure); Anti-Thymocyte Globulin (Drug); Rituximab (Drug); Filgrastim (Drug); Tacrolimus (Drug); Mycophenolate Mofetil (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Yago Nieto, MD,PHD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Yago Nieto, MD,PHD, Phone: 713-792-8750

Summary

The goal of this clinical research study is to find the highest tolerable dose of gemcitabine (out of 6 possible doses) that can be given in combination with busulfan and clofarabine before an allogeneic stem cell transplant. Researchers also want to learn if this combination can help to control lymphoma. The safety of this treatment will also be studied. Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants. Clofarabine and gemcitabine are designed to block the growth of cancer cells, which may cause the cancer cells to die.

Clinical Details

Official title: Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Dose (MTD) of Infusional Gemcitabine Combined With Fixed Doses of Clofarabine and Busulfan

Secondary outcome: Success Rate

Detailed description: Study Drug Administration and Pharmacokinetic (PK) Testing:

The days before you receive your stem cells are called minus days, such as Day - 2, Day -1.

The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days, such as Day +1, Day +2.

Between Days - 15 and -8, you will receive a low-level "test" dose of busulfan by vein over

about 45 minutes to 1 hour. Test doses are used to study how your body breaks down busulfan and decide the dose of busulfan that you will receive. You may receive the test dose before

Day - 8 as an outpatient in the clinic, or on Day -8 as an inpatient in the hospital.

Blood (about 1 teaspoon each time) will then be drawn for PK testing up to 11 times over the 11 hours after the busulfan test dose. PK testing measures the amount of study drug in the body at different time points. The study staff will tell you more about the PK testing schedule. A heparin lock line will be placed in your vein before the PK testing to lower the number of needle sticks needed for these draws. If for any reason it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.

On Day - 9 or Day -7, you will be admitted to the hospital and given fluids by vein to

hydrate you.

On Days - 6 and -4, you will receive gemcitabine by vein over 40-180 minutes. The dose you

receive will be based on when you join the study. The length of time it takes to infuse the gemcitabine will be based on when you join this study and the dose amount you are assigned. Up to 6 dose levels of gemcitabine will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of gemcitabine is found. After the highest dose is found, additional participants will be enrolled at that dose. The number of patients in the group that receives the highest tolerable dose will depend on how many have been enrolled in the other groups.

On Days - 6 through -3, you will receive clofarabine by vein over 1 hour, followed by your

dose of busulfan by vein over 3 hours. If for any reason you could not have the PK tests performed, you will receive the standard busulfan dose on these days.

On Days - 3 through -1, if your stem cell donor is not related to you, you will receive

antithymocyte globulin (ATG) by vein over 4 hours each day. ATG is designed to weaken your immune system in order to lower the risk that your body will reject the transplant. If your stem cell donor is related to you, you will not receive this drug.

Beginning on Day - 2, you will receive tacrolimus by vein over 24 hours every day until you

are able to take it by mouth. Tacrolimus is designed to weaken the immune system and lower

the risk of graft-versus-host-disease (GVHD - a reaction of the donor's immune cells against

your body). After you are able to take tacrolimus by mouth, you will take it every day for about 6 months, or until the doctor thinks it is safe to stop. On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere from about 30 minutes to several hours. After the stem cell infusion, you will begin receiving mycophenolate mofetil (MMF) by vein over about 2 hours, 2 times a day. When your doctor thinks you can tolerate taking it by mouth, you will switch to taking MMF by mouth 2 times a day with food. If you do not have GVHD between Days 40 and 60, your dose of MMF will be lowered. If you miss a dose of MMF you should tell your study doctor. You should not try to make up the dose later. If you develop GVHD, you may have to take MMF for a longer period of time. Starting 1 week after the transplant (Day +7), you will receive filgrastim (G-CSF) as an injection under the skin 1 time each day until your blood cell levels return to normal. Filgrastim is designed to make white blood cells grow, which may help to fight infections. You may be given other standard drugs to help lower the risk of side effects. You may ask the study staff for more information about how the drugs are given and their risks. Study Visits: About 30 days before receiving the stem cells, you will have computed tomography (CT) and/or positron emission tomography (PET) scans to check the status of the disease. About 4 weeks after the stem cell transplant:

- You will have a physical exam, including measurement of your height, weight, and vital

signs (blood pressure, heart rate, temperature, and breathing rate).

- You will be asked about how you are feeling and about any side effects you may be

having.

- You will be checked for possible reactions to the study treatment, including GVHD.

- Blood (about 4 tablespoons) will be drawn for routine tests, to see how the transplant

has taken, and to check the status of the disease. Follow-Up Visits: About 3, 6, and 12 months after the transplant, and then every 6 months for 4 more years:

- You will have a physical exam, including measurement of your vital signs.

- You will be asked about how you are feeling and about any side effects you may be

having.

- You will be checked for possible reactions to your treatment, including GVHD.

- Blood (about 4 tablespoons) will be drawn for routine tests, to see how well the

transplant has taken, and to check the status of the disease.

- At any point that your doctor thinks they are needed, you will have a bone marrow

aspiration and CT and/or PET scans to check the status of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle. The study staff will also stay in contact with your local doctor to find out if the disease comes back and to check how you are doing. Length of Treatment: You will be on study for about 5 years. After 1 year, there is no study specific testing you will be required to complete. Your transplant doctor will perform routine standard of care follow-up that all patients receiving allogeneic stem cell transplantation receive. You may be removed from the study early if the doctor thinks it is in your best interest, if the disease gets worse or comes back, if intolerable side effects occur, if you have graft failure (the transplanted cells do not grow), or if you are unable to follow study directions. If for any reason you want to leave the study early, you must talk to the study doctor. It may be life-threatening to leave the study after you have started to receive the study drugs but before you receive the stem cell transplant because your blood cell counts will be dangerously low. This is an investigational study. Gemcitabine and clofarabine are FDA approved and commercially available for the treatment of lymphoma. Busulfan is FDA approved and commercially available for use in stem cell transplantation. The combination of gemcitabine given in combination with busulfan and clofarabine before an allogeneic stem cell transplant is investigational. Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility

Minimum age: 12 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Age 12 to 65 years of age. 2. Patients with refractory B-cell or T-cell non-Hodgkin's lymphoma or Hodgkin's lymphoma who are eligible for allogeneic transplantation. 3. An 8/8 HLA matched (high resolution typing at A, B, C, DRB1) sibling or unrelated donor. 4. Left ventricular EF >/= 45%. 5. FEV1, FVC and corrected DLCO >/= 50%. 6. Adequate renal function, as defined by estimated serum creatinine clearance >/=50

ml/min (using the Cockcroft - Gault formula: creatinine clearance =

[(140-age)*kg/(72*serum creatinine)] * 0. 85 if female) and/or serum creatinine /=10,000 copies/mL, or >/= 2,000 IU/mL). 4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology. 5. HIV infection. 6. Active uncontrolled bacterial, viral or fungal infections. 7. Exposure to other investigational drugs within 4 weeks before enrollment. 8. Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to

Locations and Contacts

Yago Nieto, MD,PHD, Phone: 713-792-8750

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: October 2012
Last updated: June 22, 2015

Page last updated: August 23, 2015

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