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Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00617929
First received: February 15, 2008
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with clofarabine and rituximab works in treating patients after an unsuccessful stem cell transplant.


Condition Intervention Phase
Cancer
Biological: anti-thymocyte globulin
Biological: rituximab
Drug: clofarabine
Procedure: stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Donor engraftment [ Time Frame: at 42 days post transplantation ] [ Designated as safety issue: No ]
    The process of transplanted stem cells reproducing new cells.


Secondary Outcome Measures:
  • Treatment-related Death [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Number of patients who died related to the treatment in this study.

  • Time to primary neutrophil engraftment [ Time Frame: at day 42 post transplantation ] [ Designated as safety issue: No ]
    blood test shows 500 or more neutrophils in a cubic millimeter of blood

  • Overall Survival [ Time Frame: at day 100 and 1 year ] [ Designated as safety issue: No ]
    Number of patients alive from beginning of study to Day 100 and 1 year.

  • Chimerism [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    the occurrence of genetically distinct cell types in a single organism

  • Acute graft-vs-host disease [ Time Frame: Day 30-100 ] [ Designated as safety issue: No ]
    T-cells present in the donor's bone marrow at the time of transplant identify the BMT patient as "non-self' and attack the patient's skin, liver, stomach, and/or intestines.


Estimated Enrollment: 28
Study Start Date: January 2008
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Conditioning for Graft Failure
Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
Biological: anti-thymocyte globulin
administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4.
Other Name: Thymoglobulin®
Biological: rituximab
administered 375 mg/m^2 intravenously (IV) in 1 mg/mL normal saline on day -7.
Other Name: Rituxan(R)
Drug: clofarabine
administered 30 mg/m^2 intravenously (IV) over 1 hour on Days -4, -3, and -2.
Other Name: CLOLAR™
Procedure: stem cell transplantation
administered on Day 0 per institutional guidelines.

Detailed Description:

OBJECTIVES:

Primary

  • To determine the rate of sustained donor engraftment at 42 days and survival at 100 days post transplantation in patients treated with anti-thymocyte globulin, clofarabine, and rituximab.

Secondary

  • To determine incidence of treatment-related mortality at day 100 post transplantation.
  • To determine incidence of neutrophil recovery by day 42 post transplantation.
  • To determine survival at day 100 and 1 year post transplantation.
  • To determine the proportion of patients with chimerism at day 28 post transplantation.
  • To determine incidence and severity of grades II-IV acute graft-vs-host disease by day 100 post transplantation.

OUTLINE:

  • Conditioning regimen: Patients receive rituximab intravenously (IV) on day -7, anti-thymocyte globulin IV over 4-6 hours on days -6 to -4, and clofarabine IV over 1 hour on days -4 to -2.
  • Hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0. Patients may receive umbilical cord blood, peripheral blood stem cells, or bone marrow from unrelated or related donors.
  • Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral cyclosporine twice daily or cyclosporine IV every 8 hours beginning on day -3 and continuing for 100 or 180 days post transplantation followed by a taper; mycophenolate mofetil IV every 8 hours beginning on day -3 and continuing for 30 days (or 7 days after engraftment with no evidence of GVHD); and filgrastim (G-CSF) IV once daily beginning on day 1 and continuing until blood counts recover.

After completion of study therapy, patients are followed on days 100, 180, and 360.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Patient Inclusion Criteria:

  • Timing of relevant evaluations: Taking in account the need for rapid intervention, if white blood count is less than 200 on day +20, bone marrow aspirate should be performed on day +21. Unless there is an increase in absolute neutrophil count (ANC) to > 500 in the following 7 days, bone marrow aspirate should be repeated on day +28. If the white blood count is still less than 200 and bone marrow is acellular, bone marrow (BM) or peripheral blood stem cell (PBSC) donor should be reactivated and availability of cord blood (CB) units assessed. If the BM or PBSC donor is not confirmed within 14 days of the request for the donation (typically second donation from the same donor), CB unit should be used instead.

Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of donor chimerism from previous maximum or less than 25% donor beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study.

  • primary graft failure is defined as:

    • ANC < 500
    • BM < 10% on two occasions (Day +21 and Day +28)
    • Donor chimerism need not to be considered, provided there is no evidence of malignancy
  • secondary graft failure is defined as < 5% cellularity and ANC < 500 for more than 7 days any time after primary engraftment).

    • Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
    • Patients or their guardian are able and willing to provide written informed consent.

Patient Exclusion Criteria:

The presence of any of the following excludes a patient from study enrollment:

  • Uncontrolled active infection defined as more than one week with no response to appropriately chosen antibiotics
  • Evidence of recurrence of primary malignancy.
  • Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing age must use appropriate methods as described.
  • Allergy to rituximab.
  • Evidence of HIV infection or positive HIV serology.
  • Autologous recovery defined as defined as greater than 90% recipient PCR product in the competitive VNTR PCR performed on gradually increasing white blood cell count.

Donor Inclusion Criteria:

  • Related donors must be 2-75 years of age and in good health.
  • Meets match criteria
  • Able and willing to undergo cell collection procedures (bone marrow cell collection or leukapheresis)
  • Not pregnant or lactating.
  • HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
  • Patients or their guardian are able and willing to provide informed consent
  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: NCT00617929

Contacts
Contact: Jakub Tolar, M.D. 612-624-7180 tolar003@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o    612-624-2620      
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Jakub Tolar, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00617929     History of Changes
Other Study ID Numbers: 2007LS072, UMN-MT2007-07, 0707M11845
Study First Received: February 15, 2008
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
chronic myelogenous leukemia
acute lymphoblastic leukemia
chronic myeloid leukemia
lymphoblastic leukemia
acute myeloid leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic myelomonocytic leukemia
chronic neutrophilic leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
juvenile myelomonocytic leukemia
Burkitt lymphoma
rhabdomyosarcoma
myelodysplastic syndromes
Hodgkin lymphoma
lymphoblastic lymphoma
breast cancer
follicular lymphoma
mantle cell lymphoma
marginal zone lymphoma
recurrent neuroblastoma
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
recurrent small lymphocytic lymphoma
recurrent malignant testicular germ cell tumor
recurrent Wilms tumor and other childhood kidney tumors
recurrent/refractory childhood Hodgkin lymphoma
refractory hairy cell leukemia
refractory multiple myeloma

Additional relevant MeSH terms:
Antilymphocyte Serum
Clofarabine
Rituximab
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014