Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00520130
First received: August 21, 2007
Last updated: May 11, 2016
Last verified: March 2016
  Purpose

Background:

Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without an HLA tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the cancer under control before SCT. In GVHD, the patient s immune system attacks the transplanted donor cells.

This study will try to improve the results of SCT from unrelated HLA-matched donors using targeted immune-depleting chemotherapy to bring the cancer under control before transplantation and to lower the chance of graft rejection, followed by reduced-intensity transplant chemotherapy to make the procedure less toxic.

Objectives:

To evaluate the safety and effectiveness of targeted immune-depleting chemotherapy followed by reduced-intensity transplant chemotherapy in patients with advanced cancers of the blood and immune system.

To evaluate the safety and effectiveness of two different drug combinations to prevent GVHD. Both regimens have been successful in preventing GVHD, but they work by different mechanisms and affect the rebuilding of the immune system after the transplant.

Eligibility:

People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.

Design:

All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.

All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.

Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:

  • Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continuing through day 14 following SCT.
  • Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

Patients receive the donor s stem cells and immune cells 2 days after the conditioning regimen.

Patients are followed at the clinic regularly for the first 6 months after SCT, and then less often for at least 5 years. Some visits may include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.

A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.


Condition Intervention Phase
Myelodysplastic Syndrome
Hodgkin's Lymphoma
Non-Hodgkin's Disease
Acute Leukemia
Multiple Myeloma
Biological: Rituximab
Drug: Cyclosporine
Drug: Allogenic stem cell transplant (ASCT)
Drug: Conditioning Chemotherapy
Drug: TMS
Drug: FLAG
Drug: EPOCH-F
Biological: Alemtuzumab
Phase 1
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: Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To assess the effects of two biologically distinct GVHD prophylaxis regimens [ Time Frame: 1year ] [ Designated as safety issue: No ]
  • To determine and monitor incidence, organ severity and overall severity of chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess overall safety of these two regimens in this setting, and overall survival. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Study of engraftment kinetics [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 92
Study Start Date: July 2007
Estimated Study Completion Date: March 2017
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
TMS Arm
Biological: Rituximab
Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease
Drug: Allogenic stem cell transplant (ASCT)
Allogenic stem cell transplant
Drug: Conditioning Chemotherapy
Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3
Drug: TMS
Tacrolimus: 0.02 mg/kg , start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.
Drug: FLAG
Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Drug: EPOCH-F
Fludarabine:25 mg/m2 per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m2 per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m2/day CIV, days 1-4 Vincristine:0.4 mg/m2 per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m2 IV infusion over 30 minutes on day 5
Experimental: B
AC Arm
Biological: Rituximab
Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease
Drug: Cyclosporine
Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if GVHD does not develop.
Drug: Allogenic stem cell transplant (ASCT)
Allogenic stem cell transplant
Drug: Conditioning Chemotherapy
Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3
Drug: FLAG
Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy
Drug: EPOCH-F
Fludarabine:25 mg/m2 per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m2 per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m2/day CIV, days 1-4 Vincristine:0.4 mg/m2 per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m2 IV infusion over 30 minutes on day 5
Biological: Alemtuzumab
Alemtuzumab:20 mg/day IV over 8 h on days 8 to 4 pre-transplant.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • ELIGIBILITY CRITERIA RECIPIENT ON STANDARD CARE THERAPY:
  • The patient is 18 74 years of age.
  • The patient has a potentially suitable 8/8 donor if they are between the ages of 69-74 years of age or a potentially suitable 8/8 or 7/8 unrelated donor(s) in the National Marrow Registry or Other Available Registry if they are between the ages of 18-74.
  • The patient currently does not meet the protocol s eligibility/enrollment criteria for any reason.
  • There is a high likelihood that the patient, in the opinion of the PI or LAI, will meet the protocol s eligibility/enrollment criteria to proceed to transplant after standard therapy is completed.
  • The patient or legal guardian is able to give informed consent.

EXCLUSION CRITERIA RECIPIENT ON STANDARD CARE THERAPY:

  • HIV infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
  • Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00520130

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lauren M Curtis, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00520130     History of Changes
Other Study ID Numbers: 070195  07-C-0195 
Study First Received: August 21, 2007
Last Updated: May 11, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Unrelated Donors
Reduced Intensity Stem Cell Transplant
Leukemia
Lymphoma
Allogeneic Stem Cell Transplant
Myelodysplastic Syndrome
Multiple Myeloma

Additional relevant MeSH terms:
Lymphoma
Leukemia
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Alemtuzumab
Rituximab
Cyclosporins
Cyclosporine
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 26, 2016