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Palifermin With Leuprolide Acetate Versus Control for the Promotion of Immune Recovery Following Total Body Irradiation Based T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Swedish Orphan Biovitrum
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01746849
First received: December 7, 2012
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to help determine if palifermin and leuprolide acetate can help the immune system recover faster following a stem cell transplant. Blood stem cells are very young blood cells that grow in the body to become red or white blood cells or platelets. The transplant uses stem cells in the blood from another person. The donor can be a family member or a volunteer donor. This is called an allogeneic stem cell transplant.

The investigators want to see if palifermin and leuprolide acetate can help the immune system recover faster after an allogenic transplant because experiments have shown they may be able to do this.


Condition Intervention Phase
Leukemia
Multiple Myeloma
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Biological: Palifermin
Biological: Lupron
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Randomized Phase II Study of Palifermin With Leuprolide Acetate Versus Control for the Promotion of Immune Recovery Following Total Body Irradiation Based T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • a CD4+ T cell count of greater than 200 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be documented by flow cytometry performed in the clinical lab on peripheral blood.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from transplant to death of last follow-up.

  • Transplant Related Mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    TRM is defined as death at any time from the commencement of pre-transplant conditioning due to any cause other than disease relapse with the exception of automobile or other accidents.

  • Incidence of infections [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Any bacterial, viral, fungal or parasitic infection that necessitates therapy will be noted.

  • Relapse [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: palifermin with Lupron
Patients assigned to receive palifermin will receive three additional daily doses of the drug, the first approximately 6 hours after the stem cell infusion on day 0, followed by two daily doses given at 24 hour intervals on d+1 and d+2. Patients assigned to receive Lupron will receive a further 3-month depot injection approximately 3 months (+/- one week) post the first dose.
Biological: Palifermin Biological: Lupron Procedure: peripheral blood stem cell transplantation
Active Comparator: control
The control arm consists of a standard TCD (allo-HSCT) without the addition of palifermin or Lupron.
Procedure: peripheral blood stem cell transplantation

Detailed Description:

Patients will be randomized to one of two arms: palifermin with Lupron, and control. The control arm consists of a standard TCD allo-HSCT without the addition of palifermin or Lupron.

Patients randomized to receive Lupron will receive a three month depot dose 3-6 weeks prior to the start date of the pre-transplant conditioning regimen. Patients assigned to receive palifermin will receive this drug at 60mcg/kg/day IV on three consecutive days, 24 hours apart with the last dose administered no less than 24 and no more than 48 hours prior to the start of cytoreduction. The preparative regimen to be used for transplants will consist of: hyperfractionated TBI administered in 11 doses over 4 days for a total of 1375 cGy, thiotepa 5 mg/kg/day IV x 2 days and cyclophosphamide with mesna prophylaxis 60 mg/kg/day IV x 2 days. All patients will receive ATG for two doses prior to transplant, except recipients of mismatched grafts (in the GVHD vector) will receive three doses. G-CSF mobilized CD34 PBSCs obtained from the HLA compatible donor will be infused on day 0. Patients assigned to receive palifermin will receive three additional daily doses of the drug, the first approximately 6 hours after the stem cell infusion on day 0, followed by two daily doses given at 24 hour intervals on d+1 and d+2. Patients assigned to receive Lupron will receive a further 3-month depot injection approximately 3 months (+/- one week) post the first dose. Supportive care will be administered as per the BMT Service guidelines.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Treatment Portion:

  • AML in 1st remission - for patients whose AML does not have "good risk" cytogenetic features (i.e. t (8;21), t(15;17), inv 16 without c-kit mutations).
  • Secondary AML in remission
  • AML in ≥ 2nd remission
  • ALL in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL ≥ 2nd remission
  • CML failing to respond to or not tolerating imatinib, dasatinib or nilotinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.
  • Non-Hodgkins lymphoma with chemo responsive disease in any of the following categories:

intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.

b.ii. any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.

  • Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and RAEB-2
  • Chronic myelomonocytic leukemia: CMML-1 and CMML-2.
  • Patient's age is ≥18 or ≤60 years old
  • Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status ≥ 70%
  • Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.

  • Pulmonary: asymptomatic or if symptomatic, DLCO > 60% of predicted (corrected for hemoglobin)
  • Patients have a plan to receive a peripheral blood stem cell collection.
  • Patients must have no change in disease status from treatment eligibility documented by bone marrow or appropriate imaging within 30 days of transplant
  • Patient's age is ≥18 or ≤60 years old Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status ≥ 70%
  • Patients must have adequate organ function measured by:

    1. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
    2. Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 50 ml/min (measured or calculated/estimated)
  • Patients must receive a peripheral blood stem cell transplant

Exclusion Criteria:

  • Active extramedullary disease
  • Active and uncontrolled infection at time of transplantation
  • Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months.
  • Pregnant or breast feeding
  • HIV infection
  • Patient is felt to not be a candidate for TBI by the BMT service

Donor Inclusion Criteria:

  • Donor must be willing and able to undergo PBSC collection.
  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: NCT01746849

Contacts
Contact: Jenna Goldberg, MD 212-639-4828
Contact: Miguel Perales, MD 212-639-8682

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Jenna Goldberg, MD    212-639-4828      
Contact: Miguel Perales, MD    212-639-8682      
Principal Investigator: Jenna Goldberg, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Swedish Orphan Biovitrum
Investigators
Principal Investigator: Jenna Goldberg, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01746849     History of Changes
Other Study ID Numbers: 12-077
Study First Received: December 7, 2012
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
LUPRON DEPOT
PALIFERMIN
12-077

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Preleukemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Precancerous Conditions
Vascular Diseases
Leuprolide
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014