Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases

NCT00056966 | Completed Phase 1 DMC

• 2 other identifiers: 12472ACHE
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Participants in this study have a hematologic malignancy (a disorder in the bone marrow that affects the body's ability to create blood) that might benefit from receiving an allogeneic stem cell transplant (meaning the cells come from a donor) from a family member or nearly identical matched donor. The donor may either be a matched sibling, a mismatched family member, or an unrelated person. Usually these patients are given high doses of chemotherapy before receiving a stem cell transplant to keep their immune system from rejecting the donor stem cells and to kill any diseased cells that remain in the body. However, this group of patients have a high risk of developing possibly life-threatening treatment-related side effects such as infections, damage to vital organs such as lungs, liver, kidney and heart, as well as graft versus host disease (GVHD). Instead of the high dose chemotherapy and radiotherapy usually given before a transplant, this research study uses a new pre-transplant combination of three drugs, Fludarabine, Anti-CD45 and CAMPATH-1H with low dose radiotherapy. Fludarabine is a chemotherapy drug while Anti-CD45 and CAMPATH-1H are antibodies against certain types of blood cells, including those which are causing this disease. CAMPATH-1H is particularly important because it stays active in the body for a long time after it is given, which means it may work longer to prevent GVHD symptoms. Anti-CD45 may help in eradicating residual malignant cells. All these agents also help in preventing rejection of donor stem cells. This study is designed to give a less intense chemotherapy and radiotherapy, so that the life-threatening toxicities of conventional high dose chemotherapy and radiotherapy regimen can be reduced, while maintaining the ability to cure cancer.

Conditions

Hematologic Malignancy

Keywords

Acute myeloid leukemia; Acute lymphoblastic leukemia; Chronic myeloid leukemia; Non-Hodgkin's lymphoma; Hodgkin's disease; Myelodysplastic syndrome; Myeloproliferative disorders; Multiple myeloma; Severe aplastic anemia

Outcome Measures

Primary Outcomes (1)

• Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection

  100 days post transplant

Secondary Outcomes (1)

• To obtain a preliminary estimate of the efficacy of this therapy as defined by: Complete remission at day 100 and One-year disease free survival.

  100 days and 1 year post transplant

Study Arms (2)

1

EXPERIMENTAL

recipients of HLA matched sibling transplants

Drug: ANTI-CD45; Drug: CAMPATH-1H; Drug: FK506; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Stem cell infusion

2

EXPERIMENTAL

recipients of unrelated or mismatched family donor transplants

Drug: ANTI-CD45; Drug: CAMPATH-1H; Drug: FK506; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Stem cell infusion

Interventions

ANTI-CD45 DRUG

400ug/kg Day-5 through Day-2

1; 2

CAMPATH-1H DRUG

Day -8 through Day -6 Dosed per Institutional SOP

Also known as: anti-CD52, alemtuzumab

1; 2

FK506 DRUG

Day -2 through Day 30 dose adjusted to maintain level between 5-15 ng/ml.

Also known as: tacrolimus

1; 2

Fludarabine DRUG

Day-8 through Day-5 30 mg/m2

1; 2

Total Body Irradiation RADIATION

Day-1 single dose 450 cGy

1; 2

Stem cell infusion PROCEDURE

Patients will receive peripheral blood stem cells from a HLA matched or one antigen mismatched related or unrelated donor (target CD34+ cell count \>2 x 106/kg). When peripheral stem cells are unavailable or insufficient, bone marrow (target mononuclear cell count \>2 x 108/kg) will be substituted.

1; 2

Eligibility Criteria

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

You may qualify if:

• Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation:
• Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
• Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
• Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy
• Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1),
• Non Hodgkin's lymphoma, either a) Primary refractory, or b) Beyond first complete remission(CR1)
• Hodgkin's disease, either a) Primary refractory, or b) Beyond first complete remission(CR1),
• Myelodysplastic syndrome with IPSS score \> 0. (Appendix A)
• Multiple Myeloma with stage II or III disease
• Severe aplastic anemia
• Conditions that increase Treatment Related Mortality (need one or more to be eligible):
• Greater or equal to 35 years of age;
• Ejection Fraction of less than 50%;
• DLCO less than 50% or FEV1/FVC \< 80% of predicted value;
• Diabetes Mellitus;

You may not qualify if:

• Pregnant and lactating women, or women unwilling to use contraception.
• HIV positive patient
• Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)
• Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)
• Child's class C cirrhosis
• Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months)
• Patients with known allergy to rat serum products

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Hodgkin Disease; Myelodysplastic Syndromes; Myeloproliferative Disorders; Multiple Myeloma; Anemia, Aplastic

Interventions

Alemtuzumab; Tacrolimus; fludarabine; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Anemia; Bone Marrow Failure Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Malcolm K Brenner, MD

  Baylor College of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 26, 2003
• First Posted: March 27, 2003
• Study Start: November 1, 2002
• Primary Completion: May 1, 2005
• Study Completion: December 1, 2006
• Last Updated: June 29, 2012

Record last verified: 2012-06

Locations

US (2)