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

  Show Detailed Description

  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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 19, 2014