Romidepsin Maintenance After Allogeneic Stem Cell Transplantation

Peripheral T-Cell Lymphoma Clinical Trial

Official title: Romidepsin Therapy in Conditioning and Maintenance in Patients With T-Cell Malignancies Receiving Allogeneic Stem Cell Transplant

Status Recruiting

Clinical Trial Summary

The goal of this clinical research study is to learn if giving romidepsin before and after a stem cell transplant in combination with fludarabine and busulfan can help to control leukemia or lymphoma. Researchers also want to learn the highest tolerable dose of romidepsin that can be given with this combination.

The safety of this combination and the safety of giving romidepsin after a stem cell transplant will also be studied.

This is an investigational study. Romidepsin is FDA approved and commercially available for the treatment of CTCL in patients who have received at least 1 systemic (affecting the whole body) therapy before. Busulfan and fludarabine are FDA approved and commercially available for use with a stem cell transplant.

The use of the combination of romidepsin, busulfan, and fludarabine to treat the type of leukemia or lymphoma you have is considered investigational.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Clinical Trial Description

Study Parts and Study Drug Dose Levels:

If you are found to be eligible to take part in this study, you will start Part 1 of the study. During Part 1, you will receive the study drugs before having a stem cell transplant. If the disease is well controlled after the transplant and you are still eligible, you will start Part 2. During Part 2, you will continue to receive romidepsin. The study treatments given in each part are described in more detail below.

The dose of romidepsin you receive will depend on when you join this study. 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 romidepsin is found.

All participants will receive the same dose level of fludarabine. Busulfan dose levels are explained below.

Study Drug Administration and Transplant (Part 1):

The days before you receive the stem cell transplant are called minus days. The day you receive the stem cell transplant is called Day 0. The days after you receive the stem cell transplant are called plus days.

On Days -13 and -12, you will receive busulfan by vein over 3 hours. Blood (about 1 teaspoon each time) will then be drawn for pharmacokinetic (PK) testing up to 11 times over the 11 hours after the first busulfan 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. The test results will help the doctor decide what dose of busulfan you will receive during the study.

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 -7, you will be admitted to the hospital.

On Day -6 through -3, you will receive romidepsin by vein over 4 hours, fludarabine by vein over 1 hour, and then busulfan by vein over 3 hours. PK testing up to 11 times over 11 hours will also be performed on Day -6 if the doctor thinks it is needed.

If you are going to be receiving a transplant from a matched unrelated donor, you will also receive antithymocyte globulin (ATG) by vein over 4 hours on the 3 days before the transplant. This drug is designed to further weaken your immune system to reduce the risk of rejecting of the transplant.

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). Once you are able to take tacrolimus by mouth, you will take it every day for about 3 months, or until the doctor thinks it is safe to stop taking.

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.

On Days +1, +3, +6, and +11, you will receive methotrexate by vein over about 15 minutes. Methotrexate is also designed to weaken the immune system and lower the risk of GVHD.

If the doctor thinks it is needed, you will 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.

Romidepsin Maintenance Therapy (Part 2):

Starting between Day +28 and Day +100, if you are eligible for Part 2 based on the disease status, you will continue to receive romidepsin by vein over 1 hour once or twice a month. You may receive the doses at MD Anderson or at an oncologist's office close to where you live. The study doctor will discuss this with you.

Study Visits:

As a baseline test at the beginning of the study (within 7 days before starting romidepsin), blood (about 4 tablespoons) will be drawn for comparison purposes to learn if and how romidepsin may affect the disease and your immune system. If a bone marrow aspirate will be performed at this time, additional bone marrow aspirate will be collected for testing to see how romidepsin may have affected the disease and your immune system.

You will remain in the hospital for as long as the doctor thinks is needed.

Whenever your doctor thinks it is needed, blood (about 2 tablespoons) and/or urine will be collected for routine tests.

About ½-1, 3, 6, and 12 months after the transplant:

• You will have a physical exam.

• Blood (about 8 tablespoons) will be drawn to see how well the transplant has taken and to learn if and how romidepsin may have affected the disease and your immune system.

• If the doctor thinks it is needed, you will have a bone marrow aspiration 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. Additional bone marrow aspirate will be collected for testing to see how romidepsin may have affected the disease and your immune system.

The above tests/procedures may be performed sooner, if your doctor thinks they are needed. You may also have additional tests if your doctor thinks they are needed.

Before your first dose of romidepsin in Parts 1 and 2:

• You will have an electrocardiogram (EKG) to check your heart function.

• Blood (about 4 tablespoons) will be drawn to learn if and how romidepsin may have affected the disease and your immune system. Part of this blood sample will be used for a pregnancy test if you can become pregnant.

If you are in Part 2, every 2 weeks (before each dose of romidepsin), blood (about 4 tablespoons) will be drawn for routine tests. Part of this blood sample will be used for a pregnancy test if you can become pregnant. This may be repeated more often, if your doctor thinks it is needed.

If you are in Part 2, once a month:

• You will have an EKG.

• You will have a physical exam.

Part 2 participants may have the blood tests done before each romidepsin dose and monthly EKGs and physical exams performed either at MD Anderson or your local oncologist's office. If they are performed locally, the results should be sent to the study staff. You will need to return to MD Anderson to have tests and procedures performed at 3, 6, and 12 months after the transplant.

Length of Study:

You may receive up to 4 doses of romidepsin in Part 1. You may also receive chemotherapy on certain days between Day -13 and Day -3, and the stem cell transplant on Day 0. In Part 2, you may receive up to 24 cycles of romidepsin maintenance therapy as part of the study.

Your participation on the study will be over after the follow-up visits. After 1 year, you will have routine follow-up with your transplant doctor.

You may be taken off 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. ;

Related Conditions & MeSH terms

• Cutaneous T-cell Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Prolymphocytic
• Leukemia, Prolymphocytic, T-Cell
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Peripheral T-Cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• T-Large Granulocytic Leukemia
• T-Lymphoblastic Leukemia/Lymphoma
• T-Prolymphocytic Leukemia

• NCT number: NCT02512497
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Contact: The Ohio State University Comprehensive Cancer Center
• Phone: 800-293-5066
• Email: OSUCCCClinicaltrials@osumc.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: December 8, 2017
• Completion date: December 31, 2022