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Specialized Blood Cell Transplants for Cancers of the Blood and Bone Marrow

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00003838
First received: November 1, 1999
Last updated: August 23, 2014
Last verified: August 2014
  Purpose

The are a variety of cancerous diseases of the blood and bone marrow that can be potentially cured by bone marrow transplantation (BMT). Diseases like leukemia, lymphoma, and multiple myeloma are among the conditions that can be treated with BMT.

Some patients with these diseases can be treated with medical chemotherapy alone. However, patients who relapse following chemotherapy are usually not curable with additional chemotherapy treatments. The only option known to provide a potential cure if this occurs is BMT.

Allogenic transplants are cells collected from relatives of the patient. The transplant requires additional high intensity chemotherapy and radiation in order to destroy cancerous cells. In the process, many normal bone marrow cells are also destroyed. This is the reason for transplanting stem cells. The stem cells help to build new functioning bone marrow, red cells, white cells, and platelets. In addition, the immune cells from the donor are implanted into the recipient s body and help to fight off infection and kill remaining cancerous cells.

Unfortunately, the powerful doses of chemotherapy and radiation therapy associated with allogenic BMT have toxic side effects and often make BMTs too dangerous to attempt in many patients.

In order to reduce the complications of BMT, and make it a safer available option for patients with cancers of the blood and bone marrow, researchers have developed a new approach to the BMT.

In this study researchers plan to use stem cells collected from the blood stream of patient s relatives rather than from the bone marrow (blood progenitor/stem cell transplant). In addition, researchers plan to use low doses of chemotherapy and no radiation therapy to reduce side effects. The majority of the cancer killing effect will be the responsibility of the stem cell transplant rather than the chemotherapy.


Condition Intervention Phase
Hematologic Disease
Lymphoma
Multiple Myeloma
Myelodysplastic Syndrome
Myeloproliferative Disorder
Procedure: Stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-Myeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in High Risk Patients and in Patients With Debilitating Hematologic Diseases

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To evaluate engraftment by bone marrow chimerism analysis.

Secondary Outcome Measures:
  • To determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD).

Estimated Enrollment: 214
Study Start Date: February 1999
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Stem cell transplantation
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA - Recipients:

Group A: Subjects at high risk for transplant related complications and mortality as defined below:

Ages 10 to 75 (both inclusive) with a history of one of the following:

  • Treatment with dose intensive chemotherapy and/or radiotherapy
  • Previous history of allo/auto transplant
  • History of multiple myeloma or extramedullary plasmacytoma
  • Chronic disease or co-morbid medical condition including subjects with symptoms or signs of significant pulmonary disease, hepatic disease, kidney disease, cardiac disease or disease of other organ systems which would result in increased risk of morbidity or death from a standard myeloablative transplant.

Diseases to be included:

  • CML chronic phase
  • Acute lymphoblastic leukemia (ALL), all subjects in complete or partial remission.
  • AML: AML in first complete or partial remission Exceptions: AML with good risk karyotypes: AML M3 t(15:17), AML M4Eo (inv. 16), AML t(8;21). All AML in second or subsequent complete remission.
  • MDS: refractory anemia with excess blasts (RAEB), or chronic myelomonocyte leukemia (CMML).
  • Myeloproliferative diseases associated with either cytopenia or uncontrolled proliferation.
  • CLL or small lymphocytic lymphoma (SLL) with bulky or progressive disease despite prior treatment with chemotherapy which includes purine analogs.
  • NHL

A) Intermediate or high grade relapsed or progressive despite treatment with standard therapy ineligible for autologous PBSC transplant.

B) NHL intermediate or high grade relapsing despite prior autologous transplant.

C) Low grade follicular or small lymphocytic lymphoma (1) high risk patients who have relapsed following conventional chemotherapy, (2) relapsed following autologous marrow or PBSC transplant, or (3) chemo resistant disease.

D) Mantle cell lymphoma

E) NHL intermediate or high grade with concurrent BCL2 and MYC translocations who are at high risk for relapsed and who have low survival with conventional chemotherapy.

  • HD, relapsed after prior autologous transplant or after 2 or more combination chemotherapy regimens and ineligible for autologous PBSC transplant.
  • EBV driven lymphoproliferative disorders progressing despite standard therapies.
  • MM: MM subjects must be between the ages of 8 and 65 (both inclusive)

Group B: (Closed to enrollment Oct 2010) Subjects with hematologic diseases associated with reasonable longevity, shown to be curable by allogeneic BMT but where concern for a high procedural mortality with conventional BMT may delay or prevent such treatment.

Ages 8 to 80 (both inclusive) with a history of one of the following

  • PNH associated with either life-threatening thrombosis, cytopenia, transfusion dependence or recurrent and debilitating hemolytic crisis.
  • Aplastic anemia or PRCA (acquired or congenital) in subjects associated with transfusion dependence and/or neutropenia who are not candidates for or who have failed immunosuppressive therapy
  • RA or RARS MDS subjects who have associated transfusion dependence and/or neutropenia.

Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects age 8-17 years with formal consent being obtained from parents or legal guardian.

Availability of HLA identical or single HLA locus mismatched family donor

INCLUSION CRITERIA - Donor:

HLA identical or single HLA mismatched family donor

Age greater than or equal to 2 up to 80 years old

Weight greater than or equal to 18 kg

Ability of donor or guardian of donor to comprehend the investigational nature of the study and provide informed consent.

EXCLUSION CRITERIA - Recipient - any of the following:

Pregnant or lactating

Group A: age less than 10 or greater than 75 (multiple myeloma age less than 8 or greater than 65);

Group B: Age less than 8 or greater than 80 years.

ECOG performance status of 3 or more (See NIH Bone and Marrow Consortium Supportive Care Guidelines for Allogeneic Hematopoietic Stem Cell Transplant Recipients - http://intranet.cc.nih.gov/bmt/_pdf/ECOG_Karnofsky_Lansky_Scales.pdf)

Psychiatric disorder or mental deficiency severe as to make compliance with the BMT treatment unlikely and making informed consent impossible

Major anticipated illness or organ failure incompatible with survival from PBSC transplant

Diffusion capacity of carbon monoxide (DLCO) less than 40% predicted.

Left ventricular ejection fraction: less than 30%.

Serum creatinine greater than 2.5 mg/dl or creatinine clearance less than 50 cc/min by 24 hr urine collection

Serum bilirubin greater than 4 mg/dl, transaminases greater than 5x upper limit of normal,

Other malignant diseases liable to relapse or progress within 5 years.

EXCLUSION CRITERIA - Donor - any of the following:

Pregnant or lactating

Donor unfit to receive G-CSF and undergo apheresis (uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia)

HIV positive donor. Donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV I/II) will be used at the discretion of the investigator following counseling and approval from the recipient

  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: NCT00003838

Contacts
Contact: Elena J Cho (301) 594-8013 elena.cho@nih.gov
Contact: Richard W Childs, M.D. (301) 451-7128 childsr@nhlbi.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 Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Richard W Childs, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00003838     History of Changes
Obsolete Identifiers: NCT00001875
Other Study ID Numbers: 990050, 99-H-0050
Study First Received: November 1, 1999
Last Updated: August 23, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Peripheral Blood Stem Cells
Nonmyeloablative Bone Marrow Transplantation
Pure Red Cell Aplasia
Graft-Versus-Leukemia
Engraftment
Cyclophosphamide
Fludarabine
Donor Apheresis
Graft-Versus-Tumor
Graft-Versus-Host Disease
Multiple Myeloma
Extramedullary Plasmacytoma
Chronic Disease
Chronic Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Myeloproliferative Disease
Chronic Lymphocytic Leukemia
Paroxysmal Nocturnal Hemoglobinuria
Aplastic Anemia
Myelodysplastic Syndrome (MDS)
Chronic Myelomoncytic Leukemia
Non-Hodgkin's Lymphoma (NHL)
Hodgkin Disease

Additional relevant MeSH terms:
Neoplasms, Plasma Cell
Hematologic Diseases
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014