Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant

NCT ID: NCT00597714

Last Updated: 2014-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 264 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2013-11-30

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.

Conditions

Hodgkin's Disease; Non Hodgkin's Lymphoma; Myeloma; Leukemia; Myelodysplasia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A - Lymphoid Disease

Group A: Patients with a high chance of progressive lymphoid or myelomatous disease undergo Non-myeloablative Stem Cell Transplantation.

Group Type: EXPERIMENTAL

Non-myeloablative Stem Cell Transplantation

Intervention Type: DRUG

The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. Group B's prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.

Cohort B - Myeloid Disease

Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders undergo Non-myeloablative Stem Cell Transplantation.

Group Type: EXPERIMENTAL

Non-myeloablative Stem Cell Transplantation

Intervention Type: DRUG

The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. Group B's prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.

Donor

Donor priming and apheresis will include filgrastim 8 mcg/kg subcutaneously twice daily for 4 days prior to stem cell collection and continuing until pheresis is completed. Alternative mobilization strategies may be employed at the investigator's discretion.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Non-myeloablative Stem Cell Transplantation

The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. Group B's prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.

Intervention Type: DRUG

Other Intervention Names

Allogeneic Stem Cell Transplant

Eligibility Criteria

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

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

David Rizzieri, MD

OTHER

Sponsor Role: lead

Responsible Party

David Rizzieri, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David Rizzieri, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

Duke University Health System

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24269380 (View on PubMed)

Other Identifiers

Pro00003567

Identifier Type: -

Identifier Source: org_study_id