Stem Cell Transplant for Hematologic Diseases

NCT00058825 | Terminated Phase 1 Results DMC

• 1 other identifier: 8713-HIMSUM
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

Patients are being asked to participate in this study because they have a cancer in their blood, Fanconi's Anemia, or have been unsuccessfully treated for bone marrow failure such as Aplastic Anemia or Paroxysmal Nocturnal Hemoglobinuria. Any of these conditions could benefit from an allogeneic stem cell transplant using a donor that is related to the patient. Stem cells are created in the bone marrow. They grow into different types of blood cells that the patient needs, including red blood cells, white blood cells, and platelets. In a transplant, the patient's own stem cells are killed and then replaced by stem cells from the donor. Usually, patients are given very strong doses of chemotherapy prior to receiving a stem cell transplant. However, because of the patient's condition, they have a high risk of experiencing life-threatening treatment-related side-effects. Recently, some doctors have begun to use chemotherapy that does not cause as many side-effects before patients receive a transplant. This research study adds CAMPATH 1H to a low-dose chemotherapy regimen, followed by an allogeneic stem cell transplantation. We want to see whether adding CAMPATH 1H to the transplant medications helps in treating the disease. We also want to see whether there are fewer life-threatening side-effects from the treatment. CAMPATH 1H is a drug that is still being studied. CAMPATH 1H stays active in the body for a long time after patients receive it, which means it may work longer at preventing graft-versus-host-disease (GvHD) symptoms.

Conditions

Hematologic Malignancies

Keywords

Campath; stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Transplant Related Mortality (TRM)

  Percentage of patients with transplant related mortality

  100 days

Secondary Outcomes (8)

• Time in Days to ANC Engraftment

  30 days

• Donor Chimerism Engraftment of Greater Than 50%

  30 days

• Acute Graft Versus Host Disease

  100 days

• Chronic Graft Versus Host Disease

  1 year

• 2-year Relapse-free Survival

  2 years

Study Arms (1)

Stem Cell Transplant

EXPERIMENTAL

Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporine; Stem Cell Transplant; G-CSF.

Biological: Campath 1H; Drug: Fludarabine; Procedure: Stem Cell Transplant; Radiation: Total Body Irradiation (TBI); Drug: FK506 (Tacrolimus) or Cyclosporine

Interventions

Campath 1H BIOLOGICAL

Day -5 to Day -2: Campath 1H dose schedule as per institutional SOP.

Stem Cell Transplant

Fludarabine DRUG

Day -5 to Day -2: Fludarabine 30 mg/m2.

Stem Cell Transplant

Stem Cell Transplant PROCEDURE

Day 0: Donor stem cells infused.

Stem Cell Transplant

Total Body Irradiation (TBI) RADIATION

Day -6: Total body irradiation of 600 cGy as two doses without blocks at a rate of less than or equal to 10 cGy/minute.

Stem Cell Transplant

FK506 (Tacrolimus) or Cyclosporine DRUG

Day -2: FK506 or Cyclosporine as medically indicated to prevent GvHD.

Stem Cell 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 disorders; Fanconi's Anemia; Acute Myelogenous Leukemia (including secondary); Acute Lymphoblastic Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; lymphoproliferative disorders (Non-Hodgkin Lymphoma, Hairy Cell Leukemia, Chronic Lymphocytic Leukemia, and Hodgkin's Disease). Diagnosis of myelodysplastic disorders which is not good risk by IPSS: Fanconi's Anemia; Acute Myelogenous Leukemia (1st or subsequent relapse, or 2nd or subsequent CR, or refractory disease); Acute Lymphoblastic Leukemia in 2nd or subsequent remission or relapse or refractory disease; Philadelphia Chromosome-positive Chronic Myelogenous Leukemia (failed STI and interferon); Multiple Myeloma (Stage II or III); Lymphoma; Chronic Lymphocytic Leukemia (primary refractory or recurrent disease); Hodgkin's Disease (after relapse); Hemophagocytic Lymphohistiocytosis (failed chemotherapy and/or anti-viral therapy); bone marrow failure such as Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria; PNH (failed prior therapies).
• Conditions that increase treatment related mortality: (need one or more to be eligible): Age \> / = 50 years; EF of less than 45%; DLCO less than 50% or FEVI 50-75% of predicted value; Diabetes Mellitus; Renal Insufficiency (but creatinine clearance not less than 25 mL/min); Prior recent history of systemic fungal infection; 3rd or greater remission of AML or ALL; Significant Grade III or IV neurologic or hepatic toxicity from previous treatment; More than 1 year from diagnosis (CML or Myeloma patients ONLY); Multiple types of treatment regimens (equal to or more than 3); Significant Grade III or IV neurologic or hepatic toxicity from previous treatment; Prior autologous or allogeneic stem cell transplantation.
• Haploidentical family member donor. This protocol is open to patients who lack a 5/6 or 6/6 HLA antigen-matched donor. Due to the increased risk of GvHD, patients with Fanconi Anemia and a 5/6 HLA match will also be eligible.
• For this protocol, the "best" donor will be defined as a first-degree haploidentical family member who matches at the greatest number of MHC loci. Matching will be determined by Class I and Class II DNA typing. The donor should be sufficiently healthy as to not be at increased risk from the stem cell mobilization procedure. Should more than one "equally" MHC-incompatible donor be identified, other selection criteria will include: age and size of donor, CMV status, and sex. The Principal Investigator will make final decisions.
• Available healthy donor without any contraindications for donation.
• Patient and/or legal representative and/or legal guardian able to understand and sign consent.
• Age between birth and 70 years.
• Women of child-bearing potential must have a negative pregnancy test.

You may not qualify if:

• Pregnant, lactating or unwilling to use contraception.
• HIV-positive patient.
• Uncontrolled intercurrent infection.
• 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 3X upper limit of normal.
• 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
• 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

Hematologic Neoplasms

Interventions

Alemtuzumab; fludarabine; Stem Cell Transplantation; Whole-Body Irradiation; Tacrolimus; Cyclosporine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Results Point of Contact

• Title: George Carrum, MD
• Organization: Baylor College of Medicine

GCarrum@houstonmethodist.org

Study Officials

• George Carrum, MD

  Baylor College of Medicine; The Methodist Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 11, 2003
• First Posted: April 15, 2003
• Study Start: August 1, 2000
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: November 7, 2016
• Results First Posted: October 22, 2015

Record last verified: 2016-09

Locations

US (2)