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URL http://www.rockymountainbmt.com/clinical_trials/1591-Campath---Alemtuzumab-Dose-Escalation-Low-Dose-TBI-and-Fludarabine-Followed-by-HLA-Class-I-Mismatched-Donor-Stem-Cell-Transplantation-for-Patients-with-Hematologic-Malignancies---A-Multi-Center-Trial-16.html

1591 Campath - Alemtuzumab Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class I Mismatched Donor Stem Cell Transplantation for Patients with Hematologic Malignancies - A Multi-Center Trial

Principal Investigator: Peter A. McSweeney, MD

Protocol Number: RMBMT-148

Major Objectives

Minor Objectives

• Evaluate the risk of occurrence of acute and chronic GVHD
• Evaluate the risk/incidence of infections
• Determine whether engraftment can be maintained with a single dose fludarabine, DLI and continued MMF/CSP
• Evaluate the risk for disease progression and relapse

Patient Selection

Inclusion Criteria:

1. Patients 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 HSCT or with a B cell malignancy except those treatable with autologous transplant will be included:
   • Diffuse large B cell NHL– not eligible for autologous HSCT or after failed autologous HSCT.
   • Low grade NHL– with < 6 month duration of CR between courses of conventional therapy.
   • CLL –Must have failed 2 lines of conventional therapy and be refractory to fludarabine.
   • HD – Must have received and failed frontline therapy. Pts. must have failed or were not eligible for autologous transplant
   • MM – Must have received prior chemotherapy or failed autografting. An autograft immediately prior to nonmyeloablative HSCT (tandem approach) is not permitted.
   • AML – Must have < 5% marrow blasts at the time of transplant.
   • ALL – Must have <5% blasts at the time of transplant.
   • CML – Patients will be accepted beyond CP1 if they have received previous myelosuppressive chemotherapy or HSCT, and have <5% marrow blasts at time of transplant.
   • MDS –Must have failed previous myelosuppressive chemotherapy or HSCT, and have <5% marrow blasts at time of transplant
   • Myeloproliferative disorders
2. Patients < 75 years old; patients < 12 years old must be approved by the FHCRC PI (Brenda M Sandmaier, 206-667-4661). Pediatric patients with acceptably matched cord blood units can have priority on FHCRC protocol 1330.00
3. Also patients who refuse 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. Patients with related or unrelated donors for whom:
   1. the best available match is a HLA class II DRB1 and DQB1 matched donor incompatible for:
      • Any single serologically detectable class I HLA-A, -B, -C mismatch. One additional allele level class I mismatch is allowed
      • Or Any combination of 2 allele level mismatches (if typed at the molecular level).
   2. there is a likelihood of rapid disease progression while HLA typing and results of a preliminary search and the donor pool suggests that a 10/10 HLA-A,B,C,DRB1 and DQB1 matched unrelated donor will not be found
   3. there is no HLA-A, -B or -C one locus allelic mismatched related donor available
   4. there is no indication for an autologous transplantation as a treatment option

Exclusion Criteria:

1. Patients who are homozygous at the mismatched MHC class I locus
2. Life expectancy severely limited by diseases other than malignancy
3. CNS involvement with disease refractory to intrathecal chemotherapy
4. Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment
5. Female patients who are pregnant or breast feeding
6. HIV positive patients
7. Patients with non-hematological malignancies
8. Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
9. Patients with the following organ dysfunction 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.
   1. DLCO < 35% and/or receiving supplementary continuous oxygen
   2. Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients will be excluded if they are 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 >3 mg/dL, and symptomatic biliary disease.
   3. Patients with poorly controlled hypertension on multiple antihypertensives
   4. Karnofsky score < 70 for adult patients
   5. Lansky-Play Performance Score < 50 for pediatric patients

Donor Selection

Inclusion Criteria:

1. any single serologically detectable HLA-A or B or C antigen ± 1 allele
   or
2. any combination of two HLA-A, -B, or –C alleles (if prospectively typed at molecular level)

Exclusion Criteria:

1. BM donors
2. Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC
3. Donors <12 years of age