Clinical trial NCT00597714: Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant
Official title: Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin's Disease
Non Hodgkin's Lymphoma
Myeloma
Leukemia
Myelodysplasia
Keywords: Stem Cell Transplantation, Non-myeloablative
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2008-01-18
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.

Detailed description: The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have Cancer and Leukemia Group B (CALGB) performance status (PS) 0, 1, or 2; must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide peripheral blood stem cells (PBPCs) and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

Eligibility criteria: Recipient Inclusion Criteria:

* Subjects must have their diagnosis confirmed at the transplant center.
* Performance status must be Cancer and Leukemia Group B (CALGB) = 0, 1, or 2.
* Subjects must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 or better allele level match matched unrelated donor (MUD) (at A,B, C, DRB1, DQ).
* HIV negative.
* Women of child bearing potential must have a negative pregnancy test within 1 week of starting therapy.
* Subjects \> or equal to 18 years of age are eligible.
* Subjects must have a Multi Gated Acquisition Scan (MUGA) and/or Echocardiography (ECHO) or cardiac magnetic resonance (MR) and or diffusing capacity testing of the lung for carbon monoxide (DLCO) performed before transplant.
* Specific populations:

  * Group A) Subjects with a high chance of progressive lymphoid or myelomatous diseases.
  * Group B) Subjects with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders

Recipient Exclusion Criteria:

* Pregnant or lactating women.
* Subjects with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
* Subjects with uncontrolled, progressive infections.
* Subjects who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
* Subjects with active central nervous system (CNS) disease.

Donor Inclusion Criteria:

1. Donor must be capable of providing informed consent. If 14-17 years of age, a 'single patient exemption' from the local Institutional Review Board must be obtained.
2. Donor must not have any medical condition which would make mobilization or apheresis more than a minimal risk, and should have the following:

   1. Adequate cardiac function by history and physical examination. Those with a history of cardiac failure or infarction should be evaluated by a cardiologist prior to donation
   2. Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of 3000, and platelets 100,000.
3. Females should not be pregnant or lactating and have a negative serum pregnancy test within 1 week of beginning mobilization if of child bearing potential.

Primary outcomes:
measure: Disease Free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Immune Recovery
timeFrame: 1 year
measure: Progression Free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
measure: Graft Failure
timeFrame: 180 days
Other outcomes:
measure: Graft Versus Host Disease
timeFrame: 180 days
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: David Rizzieri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kanda J, Long GD, Gasparetto C, Horwitz ME, Sullivan KM, Chute JP, Morris A, Shafique M, Li Z, Chao NJ, Rizzieri DA. Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies. Biol Blood Marrow Transplant. 2014 Feb;20(2):257-63. doi: 10.1016/j.bbmt.2013.11.010. Epub 2013 Nov 20.