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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
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: June 5, 2014
Last verified: April 2014
  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
Drug: Cyclophosphamide
Biological: rituximab
Drug: Methotrexate
Drug: Sirolimus
Drug: Cyclosporine
Drug: Doxorubicin hydrochloride
Drug: Etoposide
Drug: Fludarabine phosphate
Drug: Prednisone
Drug: Vincristine sulfate
Drug: Cytarabine
Drug: Tacrolimus
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 ]

Estimated Enrollment: 105
Study Start Date: July 2007
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EPOCH-F/R
Patients receive induction chemotherapy comprising fludarabine phosphate IV over 30 minutes once daily; etoposide IV continuously, doxorubicin hydrochloride IV continuously, and vincristine IV continuously on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone on days 1-5. Patients with CD20+ disease also receive rituximab IV on day 1. All patients receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Drug: Cyclophosphamide
Given IV
Biological: rituximab
Given IV for patients with CD20-positive disease
Drug: Doxorubicin hydrochloride
Given by IV continuously
Drug: Etoposide
Given by IV continuously
Drug: Fludarabine phosphate
Given IV
Drug: Prednisone
Given orally
Drug: Vincristine sulfate
Given by IV continuously
Experimental: FLAG
Patients receive induction chemotherapy comprising fludarabine phosphate IV over 30 minutes and cytarabine IV over 4 hours on days 1-5. Patients also receive G-CSF SC beginning on day 0 and continuing until blood counts recover. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Drug: Fludarabine phosphate
Given IV
Drug: Cytarabine
Given IV
Experimental: Arm I (TMS)
Patients receive tacrolimus IV continuously or orally and oral sirolimus on days -3 to 63, followed by a taper if GVHD does not develop. Patients also receive methotrexate IV over 15 minutes on days 1, 3, 6, and 11.
Drug: Methotrexate
Given IV
Drug: Sirolimus
Given orally
Drug: Tacrolimus
Given by IV continuously or orally
Experimental: Arm II (CA)
Patients receive alemtuzumab IV over 8 hours on days -8 to -4. Patients also receive 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: Cyclosporine
Given IV
Biological: Alemtuzumab
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
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
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: NCT00520130

Contacts
Contact: Steven Z Pavletic, M.D. (301) 402-4899 sp326h@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Z Pavletic, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( 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: June 5, 2014
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:
Neoplasms, Plasma Cell
Hodgkin Disease
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Preleukemia
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
Cyclophosphamide
Cyclosporins
Cyclosporine
Cytarabine
Methotrexate
Fludarabine phosphate
Sirolimus
Everolimus

ClinicalTrials.gov processed this record on August 01, 2014