Cloretazine (VNP40101M) With Hematopoietic Cell Transplantation for Hematologic Malignancies

This study has been completed.
Sponsor:
Collaborator:
Vion Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00521859
First received: August 27, 2007
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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.

Condition Intervention Phase
Hematologic Malignancies
Drug: Cloretazine
Drug: Fludarabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dose Escalation Trial of Cloretazine (VNP40101M) and Hematopoietic Cell Transplantation for Patients With Selected, Poor-Prognosis Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • To study the highest tolerable dose of VNP40101M that can be given to patients with a form of leukemia, MDS, lymphoma, or myeloma in preparation for an autologous stem cell transplant. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: August 2007
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cloretazine + Fludarabine Drug: Cloretazine
800 mg/m^2 by vein daily
Other Name: VNP40101M
Drug: Fludarabine
25 mg/m^2 by vein daily x 5 Days
Other Names:
  • Fludarabine Phosphate
  • Fludara

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 to 65 years for autotransplant patients and age 18 to 60 years for allotransplant patients.
  2. Patients with acute leukemia/MDS or lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma (primary refractory or refractory relapse), or multiple myeloma (beyond first remission or unresponsive to therapy), not qualifying for treatment protocols of higher priority.
  3. Adequate renal function, as defined by serum creatinine <1.5 mg/dL.
  4. Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not attributable to liver disease in the case of alkaline phosphatase.
  5. Adequate pulmonary function with FEV1, FVC and DLCO >50% of expected corrected for hemoglobin.
  6. Adequate cardiac function with left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
  7. Zubrod performance status <2
  8. Patients receiving an allogeneic transplant must have a related or unrelated donor which meets departmental standards for donor selection.

Exclusion Criteria:

  1. Uncontrolled life-threatening infections
  2. HIV positive
  3. A positive Beta HCG in a woman with child bearing potential as defined as not being post-menopausal for 12 or more months or no previous surgical sterilization procedures.
  4. Any CNS involvement which has not been controlled for at least 4 weeks
  5. Patients must be at least 21 days from prior systemic therapy for their malignancy, or have improvement of all reversible toxicities to </= grade 2, whichever occurs first.
  6. Any patient receiving Antabuse
  7. Patients should be off metronidazole (Flagyl) for at least 24 hours prior to starting VNP40401M
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00521859

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Vion Pharmaceuticals
Investigators
Principal Investigator: Roy B. Jones, MD, PhD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00521859     History of Changes
Other Study ID Numbers: 2005-0844
Study First Received: August 27, 2007
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Hematologic Malignancies
Leukemia
Lymphoma
Myeloma
Hodgkin's Disease
Hematopoietic Cell Transplantation
Cloretazine
VNP40101M
Fludarabine
Fludarabine Phosphate
Fludara
ATG
Antithymocyte
Thymoglobulin

Additional relevant MeSH terms:
Neoplasms
Fludarabine
Fludarabine phosphate
Vidarabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014