Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages Up to 75 years
• All sexes
• No healthy volunteers
• Child, Adult, Older adult

Trial locations and contacts

1 site in 1 country.

About this study

Official title: Pre-administration of Rabbit Antithymocyte Globulin to Optimize Donor T-Cell Engraftment Following Reduced Intensity Allogeneic Peripheral Blood Progenitor Cell Transplantation From Matched-Related Donors

Conditions

Myeloproliferative Disorders, Kidney Cancer, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

Being tested

anti-thymocyte globulin, busulfan, cyclophosphamide, fludarabine phosphate, methotrexate

Keywords

accelerated phase CML, blastic phase CML, Philadelphia chromosome positive CML, stage I CLL, stage II CLL, stage III CLL, stage IV CLL, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, adult AML with 11q23 (MLL) abnormalities, adult CML in remission, adult ALL in remission, stage IV renal cell cancer, de novo MDS, previously treated MDS, secondary MDS, atypical CML, BCR-ABL negative, chronic myelomonocytic leukemia, MDS/myeloproliferative neoplasm, unclassifiable

Medical subject headings

Myeloproliferative Disorders, Kidney Neoplasms, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• anti-thymocyte globulinBiological

  Also called Thymoglobulin, ATG

  Anti-Thymocyte Globulin (ATG) is commercially available. The 1st vial contains 25 mg ATG, and the 2nd vial contains > 5 mL SWFI diluent. Ampuls must be refrigerated (2º C - 8º C). Do not freeze.

  Reconstitute 25 mg vial with diluent provided by manufacturer. Roll vial gently to dissolve powder. Use contents of vial within 4 hours. Dilute dosage to a final concentration of 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection. Gently invert admixture 1-2 times to mix. Use admixture solution immediately.

  Infuse the 1st dose over at least 6 hours, and subsequent doses over at least 4 hours. Infuse through a 0.22 micron in-line filter. Premeds include acetaminophen 650 mg PO, diphenhydramine 25-50 mg PO/IV, and methyprednisolone 1mg/kg at the initiation and half-way through ATG administration.

• busulfanDrug

  Commercially available in 60 mg/10 mL ampuls.

  Dilute busulfan injection in 0.9% sodium chloride injection or dextrose 5% in water. The dilution volume should be 10 times the volume of busulfan injection, ensuring that the final concentration of busulfan is ≥ 0.5 mg/mL.

  Store unopened ampuls at 2º C to 8º C. The diluted solution is stable for up to 8 hours at room temperature (25º C) but the infusion must also be completed within that 8-hour time frame. Dilution of busulfan injection in 0.9% sodium chloride is stable for up to 12 hours under refrigeration (2º C to 8º C) but the infusion must also be completed within that 12-hour time frame.

  IV Bu should be administered via a central venous catheter as a 2-hour infusion every 6 hours for 2 consecutive days for a total of 8 doses.

• cyclophosphamideDrug

  Cyclophosphamide is commercially available. Cyclophosphamide for injection is available in 2000 mg vials which are reconstituted with 100 ml sterile water for injection.

  The concentration of the reconstituted product is 20 mg/ml. The calculated dose will be diluted further in 250-500 ml of Dextrose 5% in water.

  Reconstituted solutions of lyophilized cyclophosphamide are chemically and physically stable for 24 hours at room temperature or for 6 days in the refrigerator. Specific temperatures are not provided by the manufacturer. Reconstitution of cyclophosphamide with bacteriostatic water containing benzyl alcohol preservative may result in decomposition.

  Each dose will be infused over 1-2 hr (depending on the total volume).

• fludarabine phosphateDrug

  Also called Fludara

  Fludarabine is commercially available as a white, lyophilized powder. Each vial contains 50 mg of fludarabine, 50 mg of mannitol and sodium hydroxide to adjust pH.

  Intact vials should be stored under refrigeration. Reconstituted vials are stable for 16 days and solutions diluted in D5W or NS are stable for 48 hours at room temperature or under refrigeration.

  Fludarabine should be reconstituted with 2 mL of Sterile Water for Injection, USP. Each mL of the resulting solution will contain 25 mg of fludarabine, 25 mg of mannitol, and sodium hydroxide to adjust the pH to 7-8.5. The product should be further diluted for intravenous administration in 5% Dextrose for Injection, USP or in 0.9% Sodium Chloride, USP.

  Fludarabine will be administered as an IV infusion over 30 minutes.

• methotrexateDrug

  Also called Amethopterin, MTX

  Commercially available for injection in 2 mL (2.5 mg/mL), 2 mL, 4 mL, 8 mL, 10 mL (25 mg/mL) vials, or 20 mg, 25 mg, 50 mg, or 100 mg vials for reconstitution.

  Vials requiring reconstitution should be reconstituted to a concentration of 25 mg/mL.

  Intact vials should be stored at room temperature and protected from light. Once opened, solutions containing preservatives are stable for 4 weeks at room temperature and up to 3 months refrigerated.

  Administer via slow IV push.

• tacrolimusDrug

  Also called Prograf, FK506

  Tacrolimus is commercially available as an injection (5 mg/mL; 1 mL ampuls) and as oral capsules (1 mg and 5 mg).

  Tacrolimus injection must be diluted prior to IV infusion with 0.9% sodium chloride or 5% dextrose injection to a concentration of 4-20 μg/mL. Solutions should be prepared in non-PVC plastic or glass. Tacrolimus injection and diluted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

  Oral therapy should be started as possible as per protocol and 8 to 12 hours after stopping intravenous therapy. Oral doses will be administered twice a day.

  Store tacrolimus capsules and injection at controlled room temperature, 15-30º C (59-86º F).

• nonmyeloablative allogeneic HSCTProcedure or surgery

  As demonstrated by groups in Houston, Jerusalem \& Seattle, RICT has been used to treat hematologic \& solid malignancies with related \& unrelated donors. Although adequate comparisons of RICT versus ablative alloHCT remain to be reported, the studies of RICT so far suggest that TRM is generally less than would be expected for similar patients undergoing ablative alloHCT; incidence of acute \& chronic GVHD is similar or less than ablative alloHCT; autologous hematopoietic recovery is more common than seen following ablative alloHCT if graft failure occurs; powerful GVT effects can be seen but are dependent on high levels of donor T-cell chimerism and RICT are less effective than ablative alloHCT in controlling aggressive malignancies

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation

   Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.

   Measured: Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted10 Nov 2008 (estimated)
2. Study startApr 2007
3. Primary completionJul 2010
4. Study completionMay 2012

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Publications (8)Papers the sponsor has linked to this study.
• Other trials for Myeloproliferative DisordersStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.