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URL http://www.rockymountainbmt.com/clinical_trials/1959--Campath-Alemtuzumab-Dose-Escalation-Low-Dose-TBI-and-Fludarabine-Followed-by-HLA-Class-II-Mismatched-Donor-Stem-Cell-Transplantation-For-Patients-With-Hematologic-Malignancies---A-Multicenter-Trial-35.html

1959 Campath (Alemtuzumab) Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class II Mismatched Donor Stem Cell Transplantation For Patients With Hematologic Malignancies - A Multicenter Trial

Principal Investigator: Michael B. Maris, MD

Protocol Number: RMBMT-152


Major Objectives

To determine which dose of Campath allows related and unrelated HLA class-II mismatched HCT with an incidence of grade III-IV acute GVHD <40%.

Minor Objectives

  • Incidence of graft rejection
  • Number of days of steroids ≥ 1mg/kg required before day 100 in each patient.
  • Incidence of nonrelapse mortality
  • Risk/incidence of infections
  • Immune reconstitution
  • Risk for disease progression and relapse

Patient Selection

Inclusion Criteria:

  1. The patient must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy. Patients with hematologic malignancies treatable with HCT will be included:
    1. Aggressive NHLs and Other Histologies Such as Diffuse Large B-cell NHL – not eligible for autologous HCT, not eligible for conventional myeloablative HCT, or after failed autologous HCT.
    2. Low Grade NHL – with <6 month duration of CR between courses of conventional therapy.
    3. Mantle Cell NHL – may be treated in first CR.
    4. CLL – must have failed 2 lines of conventional therapy and must be refractory to fludarabine. This includes patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog).
    5. HD – must have received and failed frontline therapy and have failed or were not eligible for autologous transplant
    6. MM – must have received prior chemotherapy or failed autografting. Following a planned autologous transplant (tandem) is allowed.
    7. AML – must have <5% marrow blasts at the time of transplant.
    8. ALL – must have <5% blasts at the time of transplant.
    9. CML – Patients will be accepted beyond CP1 if they have received previous myelosuppressive chemotherapy or HCT, and have <5% marrow blasts at time of transplant.
    10. MDS/MPD – must have failed previous myelosuppressive chemotherapy or HCT, and have <5% marrow blasts at time of transplant.
  2. Patient age < 75 years. Note: Patients <12 years old must be approved by the FHCRC PI, Brenda M Sandmaier, (206) 667-4961.
  3. Patient refuses to be treated on a conventional transplant protocol. For this inclusion, criteria transplants must be approved by both the participating institution´s patient review committee, such as the Patient Care Conference (PCC) at the FHCRC, and the FHCRC principal investigator.
  4. HLA Matching Patient with related or unrelated donors for whom:
    1. there is a likelihood of disease progression while HLA typing and results of a preliminary search and the donor pool suggest that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found.
    2. patient and donor must be matched for at least one DRB1 allele and one DQB1 allele.
    3. best available matches are HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch.
    4. there is no indication for an autologous transplantation as a treatment option.

Exclusion Criteria:

  1. Positive crossmatch between donor and recipients.
  2. Patient’s life expectancy is severely limited by diseases other than malignancy.
  3. Patient has CNS involvement with disease refractory to intrathecal chemotherapy.
  4. Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML.
  5. Patient is a fertile man or woman unwilling to use contraceptives during and for up to 12 months post treatment.
  6. Patient is a female who is pregnant or breastfeeding.
  7. Patient is HIV-positive.
  8. Patients with active non-hematologic malignancies (except non-melanoma skin cancers).
  9. Patients with a history of non-hematologic malignancies (except non-melanoma skin cancer) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a >20% risk of disease recurrence.
  10. Patient has a fungal infection with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month.
  11. Patient has the following organ dysfunction:
    1. Symptomatic coronary artery disease or ejection fraction <35% or other cardiac failure requiring therapy. Ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease.
    2. DLCO <35% TLC <30%, FEV1 <30% and/or receiving supplementary continuous oxygen.
    3. Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension. The patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3mg/dL, and symptomatic biliary disease.
  12. Patient has poorly controlled hypertension and on multiple antihypertensives.
  13. Karnofsky Performance Score <70 for adult patients.
  14. Lansky Play-Performance Score <70 for pediatric patients.
  15. Patient received cytotoxic agents for “cytoreduction” within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning. (Exceptions are hydoxyurea and imatinib mesylate.)

Donor Selection

Inclusion Criteria:

  1. For HLA matching inclusion criteria, see Patient Inclusion Criteria, section 7A4a-d.
  2. Only PBSC will be permitted as a HSC source on this protocol.

Exclusion Criteria:

  1. Marrow donors.
  2. Positive crossmatch between donor and recipient.
  3. Donor is HIV-positive and/or has a medical condition that would result in increased risk for G-CSF mobilization and harvest of PBSC.
  4. Donor age <12 years.