Cloretazine (VNP40101M) With Hematopoietic Cell Transplantation for Hematologic Malignancies
Condition: Hematologic Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Primary:

      Define the maximal tolerated dose (MTD) of VNP40401M when given with hematopoietic cell
      transplantation (HCT)

      Secondary:

        -  Describe the change in pharmacokinetic (PK) parameters with increasing doses of drug.

        -  Describe and estimate the frequency of > Grade 3 non-hematologic/non-infectious
           toxicities at the MTD.

        -  Report the efficacy of the regimen.

        -  Evaluate the rate of engraftment for the regimen.
    

Detailed description: 
      An autologous transplant uses the recipient's own stem cells, from the blood and bone marrow,
      for infusion.

      VNP40101M is a chemotherapy drug designed to interfere with the growth and development of
      cancer cells, by binding to structures within cancer cells. This drug, given in higher doses,
      causes lowering of blood cells. Chemotherapy is commonly given to patients before a stem cell
      transplantation to help kill more cancer cells. After receiving this drug, stem cells are
      transfused (given gradually) to allow re-growth of the blood cells.

      Before you can start treatment on this study, you will have what are called "screening
      tests." These tests will help the doctor decide if you are eligible to take part in this
      study. You will have blood drawn (about 3 tablespoons) for routine tests. You will have a
      physical exam, including measurement of your vital signs (blood pressure, heart rate,
      temperature, and breathing rate). You will have a bone marrow biopsy. To collect a bone
      marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount
      of marrow and bone is withdrawn through a large needle. You will have a chest x-ray and
      computed tomography (CT) and positron emission tomography (PET) scans, if required, to
      measure your tumor. You will have a lung function test and an electrocardiogram (ECG-a test
      to measure the electrical activity of the heart). Women who are able to have children must
      have a negative blood or urine pregnancy test. If you will have a blood pregnancy test it
      will be done with routine blood tests.

      Before you receive treatment on this study, you will have apheresis done to collect some of
      your stem cells. Apheresis is the process of removing part of the blood (such as platelets or
      white blood cells) from the body in order to remove certain elements, such as stem cells.
      Then the rest of the blood is returned back to the body. Your stem cells will be put back in
      your body after you finish treatment with VNP40101M. Apheresis will be done by a major vein
      through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible
      tube that will be placed into a large vein while you are under local anesthesia. The details
      of apheresis as well as the CVC will be described in separate consent forms. Your doctor will
      explain these procedures to you in more detail, and you will be required to sign a separate
      consent form for each procedure.

      If you are found to be eligible to take part in this study, you will receive a dose of
      VNP40101M. The dose you receive will depend on when you enrolled in this study. The dose that
      you receive will remain the same throughout this study. Researchers will continue to enroll
      patients at the next highest dose level until the highest tolerable dose is found.

      About 1 week after your stem cells are collected, you will be admitted to the hospital. You
      will stay in the hospital for about 3 weeks. You will then receive VNP40101M by a CVC over 6
      hours.

      Two days after you receive VNP40101M, the autologous stem cells (blood or bone marrow) will
      then be given to you by your CVC. You will receive G-CSF as an injection just under your skin
      daily, starting 1 week after your transplantation, which will help your blood cell levels
      return to normal.

      You will then have blood drawn (about 5 tablespoons) for PK testing to measure the levels of
      VNP40101M in your blood. These samples will be drawn through a heparin lock, which will be in
      place for 24 hours after the study treatment is complete. A heparin lock is a small tube
      connected to a CVC in a vein in the arm for easy access. The heparin lock will be removed
      after these samples are received.

      After you are released from the hospital, you will be required to stay in the Houston area
      for up to 1 month after the transplantation or until you are no longer experiencing any
      intolerable side effects. You will be asked to return to M. D. Anderson between 2-4 months
      following transplantation so that any late side effects of the study drug can be observed.

      As part of standard care, you will have blood tests (about 3 tablespoons) for routine tests.
      Your health status will be followed-up to continue to check on the status of the disease. You
      will have a computed tomography scan and PET scan. You will also have a bone marrow biopsy.

      If the disease gets worse or you experience any intolerable side effects, you will be taken
      off this study.

      THIS IS AN INVESTIGATIONAL STUDY. VNP40101M is not FDA approved or commercially available. It
      is authorized for use in research only.

      Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): Cloretazine; Fludarabine
Intervention type(s): Drug; Drug
Intervention description(s): 800 mg/m^2 by vein daily; 25 mg/m^2 by vein daily x 5 Days
Other intervention name(s): VNP40101M; Fludarabine Phosphate; Fludara
Intervention MeSH terms: Fludarabine; Fludarabine phosphate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematologic Malignancies; Leukemia; Lymphoma; Myeloma; Hodgkin's Disease; Hematopoietic Cell Transplantation; Cloretazine; VNP40101M; Fludarabine; Fludarabine Phosphate; Fludara; ATG; Antithymocyte; Thymoglobulin