Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies

NCT00824135 | Completed Phase 1 DMC

• 2 other identifiers: REFLEXNCI-2011-03677
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with refractory hematologic malignancies including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. The investigators institution has utilized mismatched family member donors for these patients for several reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor trans-plantation averages 3 to 4 months; (3) the alloimmune reactivity of natural killer (NK) cells following haploidentical HSCT has been shown to reduce relapse rates in certain patient groups; and, (4) no other curative treatment options are available. In the present trial, the investigators propose a novel conditioning regimen using clofarabine in an effort to enhance cytotoxicity while simultaneously reducing regimen related toxicity. In this phase I trial, the goal is to determine the maximum tolerated dose (MTD) of clofarabine when used in combination with melphalan and thiotepa pre-transplant.

Conditions

Hematologic Malignancies

Keywords

Stem Cell Transplantation, Hematopoietic; Peripheral Blood Stem Cell Transplantation; Maximal Tolerated Dose; Clofarabine; Hematological Malignancies; Apheresis

Outcome Measures

Primary Outcomes (1)

• To determine the MTD and DLT of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical HSCT with an engineered graft depleted of CD3+ cells obtained by negative selection with OKT3 on the CliniMACS system.

  30 days

Study Arms (1)

1

EXPERIMENTAL

Drug: Clofarabine; Procedure: Stem Cell Transplantation, Hematopoietic; Other: OKT3; Drug: Thiotepa; Drug: Melphalan; Drug: Mycophenolate mofetil; Drug: Rituximab; Other: G-CSF

Interventions

Clofarabine DRUG

One dose intravenously every 24 hrs for five days total. Dose level 1 Clofarabine 40 mg/m2/day intravenous Dose level 2 Clofarabine 45 mg/m2/day intravenous Dose Level 3 Clofarabine 50 mg/m2/day intravenous

1

Stem Cell Transplantation, Hematopoietic PROCEDURE

Haploidentical Hematopoietic Stem Cell Transplantation (two infusions, one on day 0 and the other on day +1)

1

OKT3 OTHER

Start at 0.0125 mg/kg intravenous once a day, taper dose down incrementally and discontinue after 17 days total Muromonab-CD3

Also known as: Orthoclone OKT3

1

Thiotepa DRUG

5 mg/kg/day intravenous every 12 hours (2 doses total)

1

Melphalan DRUG

60mg/m2 intravenous every 12 hours for 2 doses total.

1

Mycophenolate mofetil DRUG

Mycophenolate mofetil 600 mg/m2 intravenous two times a day (continue for approximately 2 months or as clinically indicated)

Also known as: MMF, CellCept

1

Rituximab DRUG

375 mg/m2 intravenous for 1 dose total

Also known as: Rituxin

1

G-CSF OTHER

G-CSF 5 mcg/kg/day subcutaneous or intravenous until ANC greater than 2.000/mm3 for 2 consecutive days and then as clinically indicated.

1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age less than or equal to 21 years old; may be greater than 21 years old if a previously treated St. Jude patient and within 3 years of completion of most recent prior disease specific therapy.
• One of the following refractory hematologic malignancies (chemoresistant relapse or primary induction failure) or diagnoses:
• ALL
• AML (\>25% blasts in the bone marrow)
• secondary AML/MDS
• CML in accelerated phase or blast crisis
• juvenile myelomonocytic leukemia (JMML)
• myelodysplastic syndrome (MDS)
• Hodgkin or non-Hodgkin lymphoma (NHL) with residual or recurrent disease following autologous HSCT, who are unable to undergo autologous HSCT due to chemo-resistant disease or inability to have an acceptable quantity of tumor-free stem cells collected (\> 1 x 108 TNC/kg marrow or \> 1 x 106 CD34+/kg PBS
• patients with a hematologic malignancy who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of medical faculty (Division of Bone Marrow Transplantation and Cellular Therapy) makes standard myeloablation prohibitive
• Does not have any other active malignancy other than the one for which this transplant is indicated
• Cardiac shortening fraction greater than or equal to 25%
• For pediatric patients, creatinine clearance greater than or equal to 90 ml/min/1.73 m2 according to the Schwartz formula for estimated GFR (ml/min/1.73m2) = k\*height (cm)/serum creatinine (mg/dL). k is a proportionality constant that varies with age and is a function of urinary creatinine clearance per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 for adolescent boys
• For adolescent or adult patients, serum creatinine 1.0 mg/dL; if serum creatinine 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where predicted GFR (ml/min/1.73 m2) = 186 x (serum creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)
• Forced vital capacity (FVC) greater than or equal to 40% of predicted value or pulse oximetry greater than or equal to 92% on room air.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38119, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Clofarabine; Hematopoietic Stem Cell Transplantation; Muromonab-CD3; Thiotepa; Melphalan; Mycophenolic Acid; Rituximab; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Immunoglobulin G; Immunoglobulin Isotypes; Serum Globulins; Globulins; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Brandon Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2009
• First Posted: January 16, 2009
• Study Start: January 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2016
• Last Updated: January 2, 2017

Record last verified: 2016-12

Locations

US (1)