Reduced Intensity Conditioning With Clofarabine, Antithymocyte Globulin (ATG), Total Lymphoid Irradiation (TLI) Followed by Allogeneic Stem Cell Transplant

NCT00697684 | Completed Phase 1 DMC

• 1 other identifier: 07-384
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

This study will examine the safety of clofarabine, TLI and ATG as a reduced conditioning regimen prior to allogeneic transplantation. The impact of the conditioning regimen on the presence of the circulating regulatory as compared to activated T cell populations will be assessed.The recovery of DC populations post-transplant will be examined, along with the effect of the regimen on disease free and overall survival.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Relapsed/Refractory Chronic Lymphocytic Leukemia; Relapsed/Refractory Non Hodgkin's Lymphoma; Hodgkins Disease; Relapsed Refractory Multiple Myeloma

Keywords

Reduced Intensity Allogeneic Stem Cell Transplant; Clofarabine; Rabbit Antithymocyte Globulin; Total Lymphoid Radiation

Outcome Measures

Primary Outcomes (1)

• To assess the toxicity and donor engraftment following treatment with a reduced intensity preparative regimen consisting of clofarabine, rabbit antithymocyte globulin (ATG), and total lymphoid irradiation followed by the infusion of allogeneic stem cells

  30 days

Secondary Outcomes (3)

• To determine the incidence of acute and chronic graft versus host disease following clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation.

  1 year

• 2. To evaluate the nature of immunologic reconstitution in patients treated clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation. The impact of the regimen on the phenotypic and functional characteristics of dendritic cell

  1 year

• To determine the disease free survival and overall survival of patients undergoing allogeneic transplantation following following clofarabine, rabbit ATG, and total lymphoid irradiation.

  Patient lifetime

Study Arms (4)

Cohort 1

NO INTERVENTION

Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).

Cohort 2

EXPERIMENTAL

Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).

Drug: Antithymocyte Globulin; Drug: Clofarabine

Cohort 3

EXPERIMENTAL

Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 30mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 150 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).

Drug: Antithymocyte Globulin; Drug: Clofarabine

Cohort 4

EXPERIMENTAL

Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 40mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 200 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).

Drug: Antithymocyte Globulin; Drug: Clofarabine

Interventions

Antithymocyte Globulin DRUG

Cohort 2; Cohort 3; Cohort 4

Clofarabine DRUG

Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).

Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a)acute myeloid leukemia exclusive of patients in first complete remission with good risk cytogenetics (translocation 8,21,translocation 15, 17 or inversion 16); B)myelodysplastic syndrome; c)acute lymphocytic leukemia exclusive of patients in first remission without negative prognostic markers; d) relapsed or refractory nonHodgkin's lymphoma or Hodgkin's disease; e)relapsed or refractory multiple myeloma or f)relapsed or refractory chronic lymphocytic leukemia.
• Patients who are considered appropriate for reduced intensity transplantation must present with at least one of the following: A. Age over 50 B. History of a prior hematopoietic stem cell transplant C. Patient with compromised organ function or comorbid conditioning such that a standard ablative transplant would be considered high risk. D. Patient with low grade Lymphoma or CLL for which reduced intensity transplant would be the optimal therapy compared to an ablative regimen
• Patients will have a related or unrelated donor matched at 5/6 or 6/6 HLA loci.
• Patients must be greater than or equal to 18 years old, and younger than or equal to 75 years old to participate in the study.
• Patients must have ECOG performance status of 0-2
• Pulmonary function tests demonstrate DLCO (adjusted for Hgb)\>50% predicted
• Cardiac ejection fraction \>40%
• Laboratories:
• Bilirubin less than or equal to 1.5mg/dL x ULN
• AST/ALT/Alkaline Phosphatase less than or equal to 2.5x ULN
• Serum creatinine less than or equal to 1.0mg/dL; if serum creatinine \> 1.0MG/dL, then the estimated glomerular filtration rate (GFR) must be \>60mL/min/1.73m\^2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GRF (ml/min/1.73m\^2)=186x (serum creatinine)\^1.154x(age in years)\^-0.203x(0.742 if patient is female) x (1.212 if patient is black)
• Patients with serologic evidence of hepatitis B or C exposure will undergo liver biopsy to assess for presence of active hepatitis or fibrosis and quantification of risk of proceeding with transplant.
• \. All patients must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. All patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines.
• \. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• \. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

You may not qualify if:

• Patients who are HIV+ will be excluded.
• Patients must not have serious intercurrent illness such as uncontrolled systemic infection or significant organ compromise which significantly increases the risk of undergoing allogeneic transplantation.
• Pregnant and lactating women will be excluded.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma

Interventions

Antilymphocyte Serum; Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; 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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• David E Avigan, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 12, 2008
• First Posted: June 16, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2020
• Study Completion: November 1, 2023
• Last Updated: November 28, 2023

Record last verified: 2023-11

Locations

US (2)