Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00038857
First received: June 5, 2002
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

Donor:

This clinical study will evaluate the feasibility of a purified CD34 peripheral blood progenitor cell (PBPC) transplants in patients with hematological malignancies.

The primary objectives of the study are to evaluate the recipient obtaining donor derived neutrophil engraftment and the incidence of acute graft versus host disease [GvHD] (grade III-IV).

Secondary objectives include assessments of recipient having donor derived platelet engraftment, incidence of graft failure and chronic GvHD, overall and disease free survival, clinical safety and device performance of the CliniMACS CD34 selection device.


Condition Intervention Phase
Leukemia
Lymphoma
Procedure: Megadose of CD34 Selected Progenitor Cells
Drug: Melphalan
Drug: Thiotepa
Drug: Fludarabine
Drug: Rabbit ATG
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants With Absolute Neutrophil Count Engraftment [ Time Frame: Day 0 up to Day 30 ] [ Designated as safety issue: No ]
    Absolute neutrophil engraftment defined as first of 3 consecutive days with Absolute neutrophil count (ANC) equal to or more than 0.5 * 10^9/L. Baseline to Day 30 post transplant.


Enrollment: 29
Study Start Date: September 2001
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CD34 PBPC
CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
Procedure: Megadose of CD34 Selected Progenitor Cells
Haploidentical peripheral blood progenitor cell (PBPC) transplants on Day 0.
Drug: Melphalan
140 mg/m^2 on day -8
Other Name: Alkeran
Drug: Thiotepa
10 mg/kg on day -7
Drug: Fludarabine
160 mg/m^2 over 4 days on days -6, -5, -4, -3
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Rabbit ATG
1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
Other Names:
  • Rabbit antithymocyte globulin
  • ATG
  • rATG
  • Genzyme
  • Thymoglobulin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female recipients must have histopathologically confirmed diagnosis of hematological or lymphatic malignancy in one of the following categories:
  2. Acute Leukemia: Recipients must have acute leukemia in second or greater remission in relapse, or primary refractory disease. Acute leukemia (in first remission with poor risk factors and molecular prognosis; acute myelogenous leukemia (AML) with -5, -7, t(6:9), +8, -11q23 and Acute lymphoblastic leukemia (ALL) with Phil+ t(9:22), t(4:11) and secondary remission inclusive).
  3. Chronic myelogenous leukemia: Chronic Myeloid Leukemia (CML) in accelerated phase, blast crisis or second chronic phase.
  4. Myelodysplastic syndrome (in high and intermediate risk categories) - marrow blast > 10% on differential.
  5. Non-Hodgkin's lymphoma in relapse
  6. Refractory chronic lymphoid leukemia (CLL) - refractory to fludarabine based regimen, unrelated donor and haploidentical only
  7. The recipient must be <=60 years old at time of registration.
  8. The recipient must have a related donor haploidentical for human leukocyte antigen (HLA), A, B, C, or DR loci. They may be partial matched on the other haplotype.
  9. Recovery from prior therapy, chemotherapy, or radiotherapy, as defined by: Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2; have recovered from the toxicity of prior major chemotherapy at the start of the preparative regimen on this protocol
  10. Adequate cardiac and pulmonary function (Left ventricular ejection fraction (LVEF) >45%, Carbon Monoxide Diffusing Capacity (DL CO)>50% corrected for hemoglobin)
  11. Serum creatinine <1.5 mg/dL or creatinine clearance >50 ml/min for those above serum creatinine of 1.5; serum bilirubin <2.0 mg/dL; Aspartate transaminase (AST)/alanine aminotransferase (ALT) <2* Upper limits of normal (ULN) (unless secondary to disease)
  12. Females of childbearing potential must have a negative serum or urine beta-HCG test within three weeks of registration. Patients will be informed of the risk of not receiving adequate contraception.
  13. No prior cancer within five years with the exception of surgically cured non-melanoma skin cancer or in situ cancer of the cervix
  14. The recipient and/or the recipient's legal guardian must have been informed of the investigational nature of this study and have signed a consent form which is in accordance with Federal guidelines and the guidelines of the participating institution.
  15. Donor age must be 4-80 years and weight greater than 20 kg.
  16. Medical history and physical examination confirm good health status as defined by institutional standards
  17. Seronegative for HIV Ag, HIV 1+2 Ab, Human T Cell Leukemia Virus (HTLV) I/II Ab, HbsAg, HbcAb (IgM [combination screening test] and IgG), HCV, RPR for syphilis within 30 days of apheresis collection - If positive for Hepatitis B or C or syphilis, the recipient must be notified - the recipient may proceed if PI, recipient and donor agree and there is no substitute donor
  18. HLA matching criteria
  19. Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization
  20. Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate
  21. Agreeable to second donation of PBPC (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant
  22. The donor, or legal guardian greater than 18 years of age, must have been informed of the investigational nature of this study and have signed a consent form in accordance with Federal Guidelines and the guidelines of the participating institution. If the donor is less than 18 years of age, parent or legal guardian consent must be obtained.
  23. The prospective donor will be screened for cytomegalovirus (CMV) seroreactivity and a seronegative donor will be utilized if available when the patient is seronegative.

Exclusion Criteria:

  1. Participation in other clinical trials which involve investigational drugs or devices that might influence the endpoints of this study
  2. Evidence of active hepatitis (B and/or C) or cirrhosis
  3. Neither the recipient nor the donor may be HIV positive
  4. Presence of any other active, uncontrolled bacterial, viral or fungal infection.
  5. Uncontrolled central nervous system (CNS) involvement with tumor cells
  6. Documented allergy to murine proteins or iron dextran
  7. The recipient is a lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control.
  8. Severe end-organ dysfunctions, particularly neurologic deficits detectable by clinical examination or significant intellectual impairment in metabolic disorders
  9. Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) or hepatitis (on screening).
  10. Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.
  11. Factors that place the donor at increased risk for complications from leukapheresis or G-CSF therapy such as pulmonary hypertension, coronary artery disease, peripheral vascular disease, cerebral vascular disease.
  12. Lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control.
  13. Donors who are hepatitis positive, Human T-cell lymphotropic virus type I (HTLVI) positive need consent of Principal Investigator and determination that this is the best donor.
  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: NCT00038857

Locations
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Richard E. Champlin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00038857     History of Changes
Other Study ID Numbers: ID01-220
Study First Received: June 5, 2002
Results First Received: June 21, 2012
Last Updated: August 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Chronic Lymphocytic Leukemia
Leukemia
Lymphoma
Non Hodgkin's Lymphoma
T cell depletion
CD34 selected progenitors cell
GVHD

Additional relevant MeSH terms:
Leukemia
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Melphalan
Thiotepa
Fludarabine phosphate
Fludarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 21, 2014