Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath

NCT00580034 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00009528
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic transplantation is used to treat many malignant and non-malignant diseases, though the potential toxicities of the procedure remain high. We and others have shown that a less toxic preparative regimen allows reliable allogeneic engraftment for allogeneic transplantation. The primary purpose of this treatment trial is to follow patients undergoing allogeneic transplantation for long term outcomes. The regimen used has been tested in our prior phase I / II trial which has completed accrual. The issues of engraftment and rate of graft versus host disease have been answered and our success has led to this regimen being a standard approach for less toxic allogeneic therapy.

Conditions

Lymphoma; Myeloma; Leukemia; Myelodysplasia; Solid Tumors

Keywords

Allogeneic Stem Cell Transplantation, Campath, HLA-Matched

Outcome Measures

Primary Outcomes (2)

• Toxicity

  Acute graft versus host disease (GVHD) was graded according to the consensus criteria and common terminology criteria (CTC) v3.0 was used for all other toxicities. Recognizing that acute GVHD pathology in the non-ablative and donor lymphocyte infusion (DLI) setting may occur late, we tabulated skin, gut and liver toxicity consistent with acute GVHD (aGVHD) at anytime in the year following the infusion as aGVHD. Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently.

  1 year

• Overall Survival (OS)

  Estimate toxicity and overall survival rates in subjects treated with a non-myeloablative preparative regimen followed by matched related allogeneic stem cells for allogeneic transplantation.

  8 years

Secondary Outcomes (1)

• Response

  2 years

Study Arms (2)

Campath Purged Non-myeloablative ASCT

EXPERIMENTAL

Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors

Drug: Campath Purged Non-myeloablative ASCT

Donor Apheresis

OTHER

Donor must be a sibling, half sibling, parent, child or first cousin familial relationship and 3-5/6 Human Leukocyte Antigen matched related to subject. They must not have any medical condition which would make apheresis and G-CSF administration more than a minimal risk, and should have the following: 1. Adequate cardiac function by history and physical examination 2. bilirubin and hepatic transaminases \< 2.5 x upper limit of normal 3. normal hematologic parameters Females should have a negative serum pregnancy test.

Procedure: Donor Apheresis

Interventions

Campath Purged Non-myeloablative ASCT DRUG

Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.

Campath Purged Non-myeloablative ASCT

Donor Apheresis PROCEDURE

Donor will receive Granulocyte colony-stimulating factor (G-CSF) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). Granulocyte-macrophage colony-stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneous or similar growth factor for donor mobilization. Donors will receive at least 3-6 doses of daily growth factor until adequate cells are mobilized.

Donor Apheresis

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have their pathology reviewed and the diagnosis confirmed.
• Performance status (PS) must be Cancer and Leukemia Group B (CALGB) PS 0, 1, or 2
• Patients must have a 3-5/6 Human leukocyte antigen (HLA)-matched related donor who is evaluated and deemed able to provide peripheral blood progenitor cells (PBPCs) and/or marrow by the transplant team.
• HIV antibody negative.
• Patients must test negative for serum beta-human chorionic gonadotropin (hCG) and must agree to use some form of adequate birth control during the periods they receive chemotherapy and any post-chemotherapy medications related to the transplant.
• Patients must be 17 years of age or greater.
• Patients must also have a resting Multi Gated Acquisition Scan (MUGA) and/or echocardiography (ECHO) and pulmonary function tests (PFTs) with testing of diffusing capacity of the lung for carbon monoxide (DLCO) performed before transplant and found to be acceptable according to the treating institution's guidelines. The required minimum standards include MUGA and/or ECHO showing an ejection fraction (EF) of 40% and PFTs showing DLCO of 40%. Those with an EF 40-50%, undergo cardiac evaluation and consultation. Also, those with DLCO 40-50%, undergo pulmonary evaluation and consultation.
• Specific populations for each disease category:
• Hematologic malignancies Those with high risk or relapsed hematologic malignancy (including myeloid and lymphoid leukemias and lymphomas, myeloma or myelomatous like diseases, myeloproliferative disease, myelodysplasia). Those with good risk disease (first remission acute myeloid leukemia (AML) with myelomonocytic together with bone marrow eosinophilia (M4eos) - inversions in chromosome 16, promyelocytic (M3) AML with translocations in chromosomes (15;17); or translocations in chromosomes (8;21) in first remission are not eligible).
• Bone marrow failure:
• Those specifically with idiopathic or secondary moderate, severe or very severe aplastic anemia (idiopathic or secondary) according to the accepted 'Camitta criteria' would be candidates.
• Those with diseases known to lead to severe marrow failure are eligible as well. These include those with myelofibrosis or Paroxysmal nocturnal hemoglobinuria (PNH).
• Solid Tumors:
• Patients must have had a biopsy confirming disease recurrence (metastases) at some point in their history, unless the patient presented with metastatic disease, in which case the initial primary site biopsy is adequate.
• Patients with renal cell cancer, or melanoma will be eligible for this approach at this time. Patients will have had documented metastatic disease at some time in the past. Patients who are in remission or with residual disease after prior therapy for their metastatic disease are eligible, as there is no accepted cure for these patients with metastatic disease.

You may not qualify if:

• Pregnant or lactating women,
• Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol, and
• Leukemia patients in first remission with good risk cytogenetics for leukemia \[t(15;17); t(8,22)\]

Sponsors & Collaborators

• David Rizzieri, MD: lead
• Miltenyi Biomedicine GmbH: collaborator

Study Sites (1)

Duke University Health Systems

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Rizzieri DA, Dev P, Long GD, Gasparetto C, Sullivan KM, Horwitz M, Chute J, Chao NJ. Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors. Bone Marrow Transplant. 2009 Feb;43(4):327-33. doi: 10.1038/bmt.2008.321. Epub 2008 Oct 13.

  PMID: 18850014 RESULT

MeSH Terms

Conditions

Lymphoma; Neoplasms, Plasma Cell; Leukemia; Anemia, Refractory, with Excess of Blasts

Condition Hierarchy (Ancestors)

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
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 24, 2007
• Study Start: February 1, 2003
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: June 3, 2014
• Results First Posted: June 3, 2014

Record last verified: 2014-05

Locations

US (1)