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

NCT00597714 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00003567
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Stem Cell Transplantation, Non-myeloablative

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  Estimate disease free survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. DFS was defined as the period of time between the day of transplantation and either disease relapse or death due to the disease. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants who were disease free at 2 years is reported by donor type.

  2 years

Secondary Outcomes (4)

• Immune Recovery

  1 year

• Progression Free Survival

  2 years

• Overall Survival

  2 years

• Graft Failure

  180 days

Other Outcomes (1)

• Graft Versus Host Disease

  180 days

Study Arms (3)

Cohort A - Lymphoid Disease

EXPERIMENTAL

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

Drug: Non-myeloablative Stem Cell Transplantation

Cohort B - Myeloid Disease

EXPERIMENTAL

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

Drug: Non-myeloablative Stem Cell Transplantation

Donor

NO INTERVENTION

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.

Interventions

Non-myeloablative Stem Cell Transplantation 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.

Also known as: Allogeneic Stem Cell Transplant

Cohort A - Lymphoid Disease; Cohort B - Myeloid Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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.
• Donor must not have any medical condition which would make mobilization or apheresis more than a minimal risk, and should have the following:
• 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
• Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of 3000, and platelets 100,000.
• 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.

Sponsors & Collaborators

• David Rizzieri, MD: lead

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 24269380 RESULT

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell; Leukemia; Anemia, Refractory, with Excess of Blasts

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: David Rizzieri, MD
• Organization: Duke University Medical Center

david.rizzieri@duke.edu

919-668-1040

Study Officials

• David Rizzieri, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 14, 2008
• First Posted: January 18, 2008
• Study Start: February 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 2, 2014
• Results First Posted: June 2, 2014

Record last verified: 2014-02

Locations

US (1)