Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

NCT00579111 | Terminated Phase 1 Results DMC

• 2 other identifiers: 19386FAB
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

Blood disorders such as leukemia or lymphoma or hemoglobinopathies can benefit from receiving an allogeneic (meaning that the cells are from a donor) stem cell transplant. Stem cells are created in the bone marrow. They grow into different types of blood cells that the body needs, including red blood cells, white blood cells, and platelets. In a transplant, the body's stem cells would be killed and then replaced by stem cells from the donor. Usually, patients are given very high doses of chemotherapy (drugs which kill cancer cells) prior to receiving a stem cell transplant. However, patients that are older, have received several prior treatments, or have other organ diseases are at a high risk of getting life-threatening treatment-related side effects from high doses of chemotherapy. Over the past several years, some doctors have begun to use lower doses of chemotherapy for preparing patients for a stem cell transplant. A condition that can occur after a stem cell transplant from a donor is Graft Versus Host Disease (GVHD). It is a rare but serious disorder that can strike persons whose immune system is suppressed and have received either a blood transfusion or a bone marrow transplant. Symptoms may include skin rash, intestinal problems similar to inflammation of the bowel and liver dysfunction. This research study uses a combination of lower-dose chemotherapy agents that is slightly different from those that have been used before. The medicines that will be used in this study are Fludarabine, Busulfan, both chemotherapy medicines, and Campath. Campath is a monoclonal antibody (a type of substance produced in the laboratory that binds to cancer cells). It helps the immune system see the cancer cell as something that needs to be destroyed. This research study will help us learn if using Fludarabine, Busulfan and Campath prior to an allogeneic stem cell transplant can provide treatment for blood disorders while decreasing the incidence of side effects.

Conditions

Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; Lymphoproliferative Disorders; Hematologic Diseases

Keywords

Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell dyscrasia; Lymphoproliferative disorders; Hematologic Diseases; Fludarabine; Busulfan; Campath; Alemtuzumab; allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Successful Donor Engraftment

  Each patient will be classified as a success or failure. A success will be defined as engraftment of at least 35% of cells 100 days after transplant.

  100 days

Secondary Outcomes (1)

• Number of Patients With Treatment Related Grade III or IV Non-hematological Toxicity

  100 days

Study Arms (2)

HLA-identical sibling transplant

EXPERIMENTAL

Recipients of HLA identical sibling stem cell transplants

Drug: Campath; Drug: Busulfan; Drug: Fludarabine; Procedure: Hematopoietic stem cell infusion; Drug: FK-506

Unrelated Matched or Single Antigen Mismatched transplant

EXPERIMENTAL

Recipients of unrelated matched or single antigen mismatched donor stem cell transplant or single antigen mismatched family donor stem cell transplants

Drug: Campath; Drug: Busulfan; Drug: Fludarabine; Procedure: Hematopoietic stem cell infusion; Drug: FK-506

Interventions

Campath DRUG

10 mg/day IV daily for 3 days on days -6 to D-4. Campath may be omitted from the conditioning regimen for patients with malignant diseases and matched related donor transplants

Also known as: Alemtuzumab

HLA-identical sibling transplant; Unrelated Matched or Single Antigen Mismatched transplant

Busulfan DRUG

3.2 mg/kg/day IV daily for 2 days, infused over 3 hours, on Day -5 and Day -4

HLA-identical sibling transplant; Unrelated Matched or Single Antigen Mismatched transplant

Fludarabine DRUG

30mg/m2/day IV daily for 4 days on Day -5 to D -2

HLA-identical sibling transplant; Unrelated Matched or Single Antigen Mismatched transplant

Hematopoietic stem cell infusion PROCEDURE

Peripheral blood stem cells when possible. Bone marrow cells will be used if peripheral blood cells are insufficient or unavailable.

HLA-identical sibling transplant; Unrelated Matched or Single Antigen Mismatched transplant

FK-506 DRUG

FK-506 at a dose of 0.03 mg/kd/day will be administered via continuous infusion over 24 hours from 4pm on Day -2 until engraftment or when the patient is able to take PO, then 0.03 mg/kg PO every 12 hours.

Also known as: Tacrolimus

HLA-identical sibling transplant; Unrelated Matched or Single Antigen Mismatched transplant

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of myelodysplastic and myeloproliferative disorders, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, multiple myeloma, plasma cell dyscrasia, lymphoproliferative disorders (non-Hodgkin lymphoma, hairy cell leukemia, chronic lymphocytic leukemia, and Hodgkin's disease) and non malignant hematologic diseases considered treatable with an allogeneic transplant including but not limited to bone marrow failure syndrome, hemoglobinopathy and severe immunodeficiency states.
• Performance status 0-2 on Zubrod scale
• Ejection fraction \> 30%
• AST/ALT and bilirubin not \> 4 times normal
• FEV1 greater than 1.0 and diffusion capacity \> 40%
• Age birth to 70 years of age
• Conditions that increase treatment related mortality (need more than one to be eligible):
• Age \> 35 years
• EF of less than 45%
• DLCO less than 50% or FEV1 50-75% of predicted value
• Diabetes mellitus
• Renal insufficiency, defined by increase in serum creatinine level of 1.5 times ULN or decrease in GFR by 25%
• Prior recent history of systemic fungal infection
• rd or greater remission of AML or ALL
• More than 1 year of diagnosis (CML or myeloma patients only)

You may not qualify if:

• Pregnant and lactating women or women unwilling to use contraception.
• HIV positive patient.
• Uncontrolled intercurrent infection.
• Refractory AML or ALL.
• Untreated blast crisis for CML.
• Uncontrolled high-grade lymphoproliferative disease/lymphoma.
• Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater).
• Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater).
• Hemodialysis dependent.
• Active Hepatitis or cirrhosis with total bilirubin, SGOT, and SGPT greater than 3 x normal.
• Serum creatinine \>2x ULN.
• Unstable cerebral vascular disease and recent hemorrhagic stroke (less than 6 months).
• Active CNS disease from hematological disorder.

Sponsors & Collaborators

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

Myeloproliferative Disorders; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma; Paraproteinemias; Lymphoproliferative Disorders; Hematologic Diseases

Interventions

Alemtuzumab; Busulfan; fludarabine; Stem Cell Transplantation; Tacrolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones

Results Point of Contact

• Title: Rammurti Kamble, MD
• Organization: Baylor

rtkamble@tmhs.org

713-394-6252

Study Officials

• Rammurti T Kamble, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: December 19, 2007
• First Posted: December 21, 2007
• Study Start: June 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: October 1, 2010
• Last Updated: May 4, 2016
• Results First Posted: August 9, 2012

Record last verified: 2016-03

Locations

US (2)