Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies

The Washington University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Leukemia, Lymphoblastic, Acute; Multiple Myeloma; Lymphocytic Leukemia, Chronic; Hodgkin Disease; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic

Treatments: Procedure: Stem Cell Transplant; Drug: AMD3100

Study type: Interventional

Funder types: Other

Identifiers

NCT00241358

03-0349

Details and patient eligibility

About

The purpose of this study is to determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.

Full description

This study will determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.

Enrollment: 92 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Donor criteria:

• Donor is 18 to 70 years of age inclusive

• If female and of child-bearing age, must be:

  • non-pregnant,
  • not breast feeding and
  • using adequate contraception

• Donor is a 6/6 HLA-matched sibling willing to donate peripheral blood stem cell for transplant

• Donor must be willing to provide written informed consent.

• Adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.

• Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation)

• Adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis

• Adequate neurologic function as defined by:

  • No evidence of a severe central or peripheral neurologic abnormality.
  • No history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication

• Must be HIV-1 & 2 antibody, HIV-1 antigen, and HTLV-I & II antibody sero-negative, by FDA licensed test.

• Must have an ECOG performance status of 0 or 1

• Must demonstrate ability to be compliant with study regimen.

• Must not have an active infection at the time of study entry

• Not have active alcohol or substance abuse within 6 months of study entry

• Not currently enrolled in another investigational agent study

• Not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation

Recipient criteria:

• 18 to 65 years of age inclusive

• Willing and has a 6/6 HLA-matched sibling willing to donate PBSC for transplant

• Provide signed informed consent

• If female and of child-bearing age, must be:

  • non-pregnant,
  • not breast feeding, and
  • using adequate contraception

Patient must have one of the following diagnoses:

• AML in 1st or subsequent remission or in relapse

• ALL in 1st or subsequent remission or in relapse

• MDS and intermediate 1 or 2, or high risk by the International Prognostic Scoring System

• CML in accelerated or second chronic phase

• NHL or HD in 2nd or greater complete remission, partial remission,or refractory relapse

• CLL Rai Stage 2-4, failing at least 2 prior regimens

• MM Stage 2-3

• Adequate cardiac function with a left ventricular ejection fraction ≥ 40%

• Adequate pulmonary function defined as:

  • No severe or symptomatic restrictive or obstructive lung disease, and
  • formal pulmonary function testing showing an forced expiratory volume at 1 second (FEV1) ≥50% of predicted and a diffusion capacity of the lung for carbon monoxide (DLCO) ≥40% of predicted, corrected for hemoglobin

• Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation)

• Adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis

• Adequate neurologic function as defined by no evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous central nervous system tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain

• No evidence of active infection at the time of the transplant preparative regimen or at the time of transplantation

• Patient must be HIV-1 & 2 antibody, HIV-1 antigen, and HTLV-I & II antibody sero-negative, by FDA licensed test

• ECOG performance status of 0 or 1

• Must demonstrate ability to be compliant with medical regimen

• Not have active alcohol or substance abuse within 6 months of study entry

• Not be concurrently enrolled on another study involving an investigational agent

• Not have any medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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92 participants in 3 patient groups

Subcutaneous (SC) Treatment Plan - Donor

Active Comparator group

Description:

* Day 1: Mobilization with 240 mcg/kg SC AMD3100 and leukopheresis * If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3.

Treatment:

Drug: AMD3100

Intravenous (IV) Treatment Plan - Donor

Experimental group

Description:

* Day -3: Mobilization with 80-480 mcg/kg/day IV AMD3100 and PK analysis * Day 1: Mobilization with 240 mcg/kg/day SC AMD3100 and leukopheresis * If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3.

Treatment:

Drug: AMD3100

Recipients

Other group

Description:

* Conditioning Regimen * Cyclophosphamide 60mg/kg/day on Days -3 and -2 * TBI 550cGy on Day -1 * GVHD prophylaxis \*Cyclosporin 3.0mg/kg/day beginning on Day -1 then tapered through Day +100 * PBSC transplant on Day 0

Treatment:

Procedure: Stem Cell Transplant