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

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ClinicalTrials.gov Identifier: NCT00003838
Recruitment Status : Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:

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 or disease Intervention/treatment Phase
Myeloproliferative Disorders Acute Myelogenous Leukemia Chronic Myelogenous Leukemia Myelodysplastic Syndrome Other: T-cell replete PBPC allograft Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 204 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : February 23, 1999
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: 1
Subjects will receive a non-myeloablative preparative regimen of cyclophosphamide 60mg/kg/d x 2 days, and fludarabine 25mg /m2 intravenously (IV) over 30 minutes daily x 5 days followed by a PBPC graft targeted to deliver >5x10^6 CD34+ cells/kg
Other: T-cell replete PBPC allograft
Subjects will receive a non-myeloablative preparative regimen of cyclophosphamide 60mg/kg/d x 2 days, and fludarabine 25mg/m2 intravenously (IV) over 30 minutes daily x 5 days with or without ATG followed by a PBPC graft targeted to deliver >5x106 CD34+ cells /kg.




Primary Outcome Measures :
  1. Transplant related mortality at 200 days. [ Time Frame: 200 days ]
    Transplant related mortality at 200 days.


Secondary Outcome Measures :
  1. To determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD). [ Time Frame: Study End ]


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Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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)
  • Mycosis fungoides, which has been shown to be amenable to allogeneic stem cell transplants.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003838


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Richard W Childs, M.D. National Heart, Lung, and Blood Institute (NHLBI)

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00003838     History of Changes
Obsolete Identifiers: NCT00001875
Other Study ID Numbers: 990050
99-H-0050
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 6, 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Graft vs. Host Disease
Peripheral Blood Stem Cells
Non-Myeloablative Bone Marrow Transplantation
Engraftment
Graft-Versus-Leukemia

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Myeloproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions