Allogeneic Transplantation From Related Haploidentical Donors

NCT00185692 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB-1337175117BMT124
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).

Conditions

Blood Cancer; Leukemia; Graft Versus Host Disease; Malignancy; CLL; NHL; Hodgkin's Disease; MDS

Outcome Measures

Primary Outcomes (1)

• Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning

  number achieving donor cell engraftment (\>95%) by day 90 after transplant.

  100 days

Secondary Outcomes (1)

• Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant

  90 days

Study Arms (1)

Transplantation of CD34+ cells

EXPERIMENTAL

Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started.

Procedure: non-myeloablative hematopoietic cell transplantation; Drug: Anti-Thymocyte Globulin; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: G-CSF; Drug: Solumedrol; Drug: Acetaminophen; Drug: Diphenydramine; Drug: Hydrocortisone

Interventions

non-myeloablative hematopoietic cell transplantation PROCEDURE

TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.

Also known as: Peripheral-blood stem-cell transplantation

Transplantation of CD34+ cells

Anti-Thymocyte Globulin DRUG

1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.

Also known as: ATG

Transplantation of CD34+ cells

Cyclosporine DRUG

6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).

Also known as: INN/BAN, USAN, CSA

Transplantation of CD34+ cells

Mycophenolate Mofetil DRUG

15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.

Also known as: MMF, CellCept

Transplantation of CD34+ cells

G-CSF DRUG

16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells

Also known as: Granulocyte colony-stimulating factor, CSF 3

Transplantation of CD34+ cells

Solumedrol DRUG

1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation

Also known as: 6-Methylprednisolone, Methylprednisolone Acetate, Methylprednisolone Sodium Succinate

Transplantation of CD34+ cells

Acetaminophen DRUG

650 mg PO, 30 minutes prior to infusion Pain reliever

Also known as: Tylenol

Transplantation of CD34+ cells

Diphenydramine DRUG

50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms

Also known as: Benadryl, Allermax, Q-Dryl, Diphen Cough

Transplantation of CD34+ cells

Hydrocortisone DRUG

100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin

Also known as: Hydrocortisone Sodium Phosphate

Transplantation of CD34+ cells

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT.
• For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants.
• Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy.
• Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted.
• AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator.
• CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase.
• MDS - All patients with MDS will be eligible for this protocol, however, those patients with \>10% blasts will require chemotherapy to reduce the blast % to \< 10%.
• SAA - Patients with severe aplastic anemia who have failed front line therapy.
• A fully HLA-identical sibling donor is not available.
• A matched unrelated donor has not been identified.
• A haploidentical related donor is available who is in good health and does not have contraindications to donation.

You may not qualify if:

• Patients with rapidly progressive intermediate or high grade NHL
• Uncontrolled CNS involvement with disease
• Fertile men
• Women unwilling to use contraceptive techniques during and for 12 months following treatment
• Females who are pregnant
• Cardiac function: ejection fraction \< 30% or cardiac failure requiring therapy
• Pulmonary: DLCO \< 40% predicted and/or receiving supplementary continuous oxygen
• Liver function abnormalities: elevation of bilirubin to \> 4 mg/dl and/or transaminases \> 3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded.
• Renal: creatinine clearance \< 50 cc/min (24 hour urine collection)
• Karnofsky performance score \< 60%
• Patients with poorly controlled hypertension.
• Documented fungal disease that persists despite treatment
• HIV positive patients.
• Hepatitis B and C positive patients will be evaluated on a case by case basis
• Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia; Graft vs Host Disease; Neoplasms; Hodgkin Disease

Interventions

Peripheral Blood Stem Cell Transplantation; Antilymphocyte Serum; Cyclosporine; Mycophenolic Acid; Granulocyte Colony-Stimulating Factor; Methylprednisolone Hemisuccinate; Methylprednisolone; Methylprednisolone Acetate; Acetaminophen; aminophylline, cycloclenbutrerol, diphenydramine, phenobarbital drug combination; Diphenhydramine; Hydrocortisone; hydrocortisone sodium phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Immune System Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Robert Lowsky
• Organization: Stanford University

rlowsky@stanford.edu

650-723-0822

Study Officials

• Robert Lowsky

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2000
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 4, 2019
• Results First Posted: January 26, 2017

Record last verified: 2015-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)