Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen

Multiple Myeloma Clinical Trial

Official title:

Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00556452
• Other study ID #: UMCC 2007.055
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 8, 2007
• Last updated: October 30, 2017
• Start date: October 2007
• Est. completion date: September 2012

Study information

• Verified date: October 2017
• Source: University of Michigan Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity conditioning (Clo/BU4 regimen) prior to transplant and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for stem cell transplant in the treatment of aggressive hematologic malignancies in subjects where more conventional approaches are failing.

Description:

Transplants with stem cells collected from the blood of an unrelated donor (allo-HSCT) are being used more commonly for many blood cancers which are not curable with more conventional methods of chemotherapy. Although allo-HSCT has great potential, there are still high risks due to infections, graft-versus-host disease (GVHD), where the donor's cells attack the recipient's tissues as foreign, and due to toxic effects of the chemotherapy drugs given to prepare (or condition) the recipient's bone marrow for transplant.

As a reduced intensity conditioning, a combination of Fludarabine and a lower dose of Busulfan (Flu/BU2) is one of the most popular regimens. Among full-intensity regimens, a combination of Fludarabine and standard-dose Busulfan (Flu/BU4) has been investigated recently and shown to be very well tolerated.

Clofarabine, similar to Fludarabine, is known to have a stronger anti-tumor effect than Fludarabine and has shown promise in treating aggressive acute leukemias. In addition, evidence is that it is well-tolerated with manageable side effects especially in older subjects. Thus replacing Fludarabine with Clofarabine in a full-intensity transplant regimen, Clo/BU4 may provide a regimen with increased anti-tumor activity without adding significant risks of toxicity.

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity regimen (Clo/BU4) and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for HSCT in the treatment for aggressive hematologic malignancies, in subjects where more conventional approaches are failing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: September 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

Inclusion Criteria:

Disease Criteria

• Acute leukemia or chronic myelogenous leukemia in blastic crisis or accelerated phase, not in remission at the time of transplant

• Myelodysplastic syndrome, with more than 5% blasts in bone marrow at the time of transplant

• Hodgkin and Non-Hodgkin Lymphomas: Not in CR in PET scan or CT scan before transplant, or relapsed within 1 year from previous remission

• CLL not in remission

• Multiple Myeloma, not in remission

• Suitable donor available (related or unrelated)

Age, Organ Function Criteria

• Age: = 70 years

• Cardiac: LV Ejection Fraction = 40% by MUGA or Echocardiogram

• Pulmonary: FEV1 and FVC = 40% predicted, and DLCO (corrected for hemoglobin) = 40% of predicted

• Renal: Adult population: 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)

• Renal: Pediatric population: serum creatinine clearance = 90 ml/min/1.73 m2 as calculated by the Schwartz formula for estimated GFR

• Hepatic: serum total bilirubin = 2.0 mg/dl and AST / ALT = ULN x 4

• Performance status: Karnofsky = 70%

Exclusion Criteria:

• Other active life-threatening cancer requiring treatment other than allo-HSCT

• HIV1 or HIV2 positive

• Uncontrolled medical or psychiatric disorder

• Uncontrolled viral or fungal infection

• Active CNS leukemia

• Non-compliant to medications

• No appropriate caregivers identified

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-Hodgkin Lymphoma
• Preleukemia

Intervention

Drug:
• Clofarabine/Busulfan x 4
Clofarabine IV (dose levels) 1st dose level: 20 mg/m2/day x 5 days 2nd dose level: 30 mg/m2/day x 5 days 3rd dose level: 40 mg/m2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days

Procedure:
• Peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Radiation:
• Total Lymphoid Irradiation
Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Locations

Country	Name	City	State
United States	University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan Cancer Center	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Regimen Related Toxicities	The incidence of non-hematological toxicities (Common Terminology Criteria for Adverse Events (CTCAE) 3.0) from initiation of conditioning to Day + 30 or toxicities after day +30, possibly, probably or definitely related to conditioning for all patients treated with Clofarabine (independent of dose level).	two years
Primary	One-year Overall Survival Rate for AML	Percent Overall Survival (OS) for at one year for subjects with Acute Myeloid Leukemia (AML).	1 year
Secondary	Two-year Overall Survival for All Cases.	Percent Overall Survival (OS) at two years for all patients.	2 years
Secondary	Five Year Overall Survival for All Cases	The number of patients alive at 5 years	five years