Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia
Intervention: Megadose of CD34 Selected Progenitor Cells; Melphalan; Thiotepa; Fludarabine; Rabbit ATG
Intervention description: Haploidentical peripheral blood progenitor cell (PBPC) transplants on Day 0.; 140 mg/m^2 on day -8; 10 mg/kg on day -7; 160 mg/m^2 over 4 days on days -6, -5, -4, -3; 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Melphalan; Thiotepa; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Maximum age: 55 Years
Healthy volunteers: No
Keywords: 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

Summary:

      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.
    

Eligibility 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.